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Hou W, Wu N, Liu Y, Tang Y, Quan Q, Luo Y, Jin C. Mpox: Global epidemic situation and countermeasures. Virulence 2025; 16:2457958. [PMID: 39921615 PMCID: PMC11810083 DOI: 10.1080/21505594.2025.2457958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 01/01/2025] [Accepted: 01/20/2025] [Indexed: 02/10/2025] Open
Abstract
Mpox, is a zoonotic disease caused by the monkeypox virus and is primarily endemic to Africa. As countries gradually stop smallpox vaccination, resistance to the smallpox virus is declining, increasing the risk of infection with mpox and other viruses. On 14 August 2024, the World Health Organization announced that the spread of mpox constituted a public health emergency of international concern. Mpox's transmission routes and symptoms are complex and pose new challenges to global health. Several vaccines (such as ACAM2000, JYNNEOS, LC16m8, and genetically engineered vaccines) and antiviral drugs (such as tecovirimat, brincidofovir, cidofovir, and varicella immunoglobulin intravenous injection) have been developed and marketed to prevent and control this disease. This review aims to introduce the epidemic situation, epidemiological characteristics, physiological and pathological characteristics, and preventive measures for mpox in detail, to provide a scientific basis for the prevention and control of mpox viruses worldwide.
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Affiliation(s)
- Wenshuang Hou
- Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
| | - Nan Wu
- Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
| | - Yanzhi Liu
- Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
| | - Yanjun Tang
- Department of Food Quality and safety, College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
| | - Quan Quan
- Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
| | - Yinghua Luo
- Department of Grass Science, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
| | - Chenghao Jin
- Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
- Department of Food Quality and safety, College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China
- National Coarse Cereals Engineering Research Center, Daqing, People’s Republic of China
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Liu C, Wang X, Zhou C, Cao X. A real-world disproportionality analysis of cidofovir from the FDA Adverse Event Reporting System (FAERS) database. Expert Opin Drug Saf 2025:1-9. [PMID: 40193180 DOI: 10.1080/14740338.2025.2490271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 03/05/2025] [Indexed: 04/10/2025]
Abstract
BACKGROUND Cidofovir, an antiviral drug used to treat cytomegalovirus retinitis in AIDS patients. While effective against several viruses, cidofovir's nephrotoxicity and other adverse events (AEs) limit its broader use. This study aims to evaluate the AE profile of cidofovir using data from the FAERS database. RESEARCH DESIGN AND METHODS An analysis of FAERS data from the first quarter of 2004 to the fourth quarter of 2023 was performed. Signal detection was conducted using four algorithms: ROR, PRR, BCPNN, and EBGM. Data were categorized by system organ classes (SOCs) and preferred terms (PTs), and the strength of association between cidofovir and AEs was assessed. RESULTS 1,874 AE reports involving 1,266 patients were identified. 'Renal and urinary disorders,' 'Infections and infestations,' and 'Immune system disorders' were the most frequently reported SOCs, with the highest signal detected for 'Renal and urinary disorders.' Off-label use was the most common PT, highlighting the importance of controlling the indication of medication in clinical practice. CONCLUSION This study identified significant signals related to cidofovir, suggesting that clinicians should carefully monitor patients, especially when using cidofovir for off-label purposes to mitigate potential risk outcomes. Further research is needed to optimize the safe and effective use of cidofovir.
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Affiliation(s)
- Chengzhi Liu
- Beijing Ophthalmology & Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xinyu Wang
- Beijing Ophthalmology & Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Chuanlie Zhou
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xusheng Cao
- Beijing Ophthalmology & Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Tiwari H, Ilyas A, Rai PK, Upadhyay S, Borkotoky S. Computational investigation of antiviral peptide interactions with Mpox DNA polymerase. In Silico Pharmacol 2025; 13:49. [PMID: 40162132 PMCID: PMC11953516 DOI: 10.1007/s40203-025-00342-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 03/18/2025] [Indexed: 04/02/2025] Open
Abstract
The Mpox DNA polymerase (DNA pol) plays a crucial role in the viral replication process, making it an ideal target for antiviral therapies. It facilitates the synthetic process of viral DNA, which is an integral stage in the life of a virus. The inhibition of the operation of Mpox DNA pol would interfere with the multiplication of the virus and help manage the disease. Peptides have emerged as a possible therapeutic alternative against viruses due to their distinct characteristics. Peptides have broad-spectrum antiviral activity, being effective against a variety of viruses. Using computational techniques, we attempted to explore the molecular details of the interaction between antiviral peptides and Mpox DNA pol. Two databases of antiviral peptides were screened in this study. This study used molecular docking, followed by molecular dynamics (MD) simulation and post-simulation binding energy predictions. From the 19 selected peptides with activity against DNA polymerases, two peptides-DRAVPe01393 and DRAVPe01399-were identified as particularly promising candidates. These peptides exhibited stable interactions with Mpox DNA pol and demonstrated good cell penetration potential as evident from the MD simulation studies. Notably, the peptides DRAVPe01399 and DRAVPe01393 have a better binding affinity of - 60.86 kcal/mol and - 47.92 kcal/mol respectively than the control ligand Cidofovir diphosphate (- 10.79 kcal/mol). These findings could lead to the development of innovative antiviral treatments to prevent monkeypox, helping global efforts to battle this emerging infectious disease.
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Affiliation(s)
- Harshit Tiwari
- Department of Biotechnology, Invertis University, Bareilly, India
| | - Ashal Ilyas
- Department of Biotechnology, Invertis University, Bareilly, India
| | - Pankaj Kumar Rai
- Department of Biotechnology, Invertis University, Bareilly, India
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Tai W, Tian C, Shi H, Chai B, Yu X, Zhuang X, Dong P, Li M, Yin Q, Feng S, Wang W, Zhang O, Liang S, Liu Y, Liu J, Zhu L, Zhao G, Tian M, Yu G, Cheng G. An mRNA vaccine against monkeypox virus inhibits infection by co-activation of humoral and cellular immune responses. Nat Commun 2025; 16:2971. [PMID: 40140411 PMCID: PMC11947304 DOI: 10.1038/s41467-025-58328-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 03/18/2025] [Indexed: 03/28/2025] Open
Abstract
The persistent monkeypox outbreaks intensify the demand for monkeypox vaccines. Based on the mRNA vaccine platform, we conduct a systematic screening of monkeypox virus (MPXV) surface proteins from two types of viral particles, extracellular enveloped viruses (EVs) and intracellular mature viruses (MVs). This screening unveils 12 important antigens with diverse levels of neutralizing immunogenicity. Further assessment reveals that the combinations of 4, 8, and 12 of these antigens, namely Mix-4, Mix-8, and Mix-12, induce varying degrees of immune protection, with Mix-12 being the most potent. This finding demonstrates the significance of not only the level but also the diversity of the neutralizing antibodies in providing potent immune protection. Additionally, we utilize a T cell-epitope enrichment strategy, analyzing the complete proteome sequence of the MPXV to predict antigenic epitope-rich regions. Integration of these epitope-rich regions into a cellular immune-targeting antigen, named MPX-EPs, showcases that a cellular immune-targeting mRNA vaccine can independently confer immune protection. Furthermore, co-immunization with Mix-12 and MPX-EPs achieves complete protection against MPXV challenge. Overall, these results suggest an effective approach to enhance the immune protection of mRNA vaccines through the specific coordination of humoral and cellular immune responses.
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MESH Headings
- Animals
- Immunity, Humoral
- Immunity, Cellular
- Mice
- Antibodies, Neutralizing/immunology
- Monkeypox virus/immunology
- mRNA Vaccines/immunology
- Female
- Mpox, Monkeypox/prevention & control
- Mpox, Monkeypox/immunology
- Antibodies, Viral/immunology
- Mice, Inbred BALB C
- Humans
- Vaccines, Synthetic/immunology
- Viral Vaccines/immunology
- Chlorocebus aethiops
- Antigens, Viral/immunology
- Epitopes, T-Lymphocyte/immunology
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Affiliation(s)
- Wanbo Tai
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China.
| | - Chongyu Tian
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China
- New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China
| | - Huicheng Shi
- New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, China
| | - Benjie Chai
- New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China
| | - Xinyang Yu
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China
| | - Xinyu Zhuang
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China
| | - Pengyuan Dong
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China
| | - Min Li
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China
| | - Qi Yin
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China
| | - Shengyong Feng
- New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China
| | - Weixiao Wang
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China
| | - Oujia Zhang
- New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China
| | - Shibo Liang
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China
| | - Yang Liu
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China
| | - Jianying Liu
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China
| | - Longchao Zhu
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China
| | - Guangyu Zhao
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
| | - Mingyao Tian
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
| | - Guocan Yu
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China.
| | - Gong Cheng
- New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China.
- Institute of Pathogenic Organisms, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
- Southwest United Graduate School, Kunming, China.
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Fetensa G, Tolossa T, Besho M, Yadesa G, Gugsa J, Tufa DG, Bati F, Duftu KB, Wakuma B. Willingness to take Mpox vaccine and associated factors among health professionals in Ethiopia: A cross-sectional study. Vaccine 2025; 49:126822. [PMID: 39892112 DOI: 10.1016/j.vaccine.2025.126822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 01/27/2025] [Accepted: 01/27/2025] [Indexed: 02/03/2025]
Abstract
BACKGROUND Monkeypox (Mpox) is vaccine preventable a viral infection declared as a public health emergency of international concern by the World Health Organization in 2022. As a response to the epidemic, vaccines against the virus are being implemented in different countries, complementing other public health interventions. However, little is known about the willingness to accept the Mpox vaccine among health professionals in Africa, notably in Ethiopia. Therefore, this study aimed to identify willingness to take the Mpox vaccine and associated factors among health professionals in Ethiopia. METHODS A national online cross-sectional study design was employed between August 31, 2024, and September 6, 2024, among health professionals in Ethiopia. The data were collected from purposively selected healthcare professionals utilizing snowball sampling to achieve a high response rate using a semi-structured online survey tool. The tool was pretested, every survey item was drafted as a must-fill, and only data with correct characters were included after removing responses with miss response for the intended questionnaire. Variables with a p-value<0.25 in the bivariable logistic regression analysis were taken as candidates for multivariable analysis. An adjusted odds ratios (AORs) with 95 % confidence interval (CI) were computed and p-value <0.05 were used to set statistically significant variables within final model. Finally, text, tables, and figures were used to present the data. RESULTS The study involved 749 health professionals. Of the participants, 637 (85 %) were males, 674 (90 %) were currently employed in urban areas, and 543 (72.5 %) had received the COVID-19 vaccine. Among all participants, 423 (56.5 %) demonstrated a good knowledge of Mpox, whereas 211 (28.2 %) expressed a willingness to get vaccinated against Mpox. Besides, recent travel to countries experiencing the Mpox outbreak (AOR = 3.21, 95 %CI:1.65-6.29), positive attitude towards the Mpox vaccine uptake (AOR = 3.08, 95 %CI:2.11-4.49), lack of access to Mpox infection information (AOR = 1.93, 95 %CI:1.05-3.55), the belief that avoiding treatment of Mpox cases would prevent self-contamination (AOR = 4.05, 95 %CI: 2.83-5.80), and prior contact with individuals diagnosed with COVID-19 (AOR = 1.57 95 %CI (1.07-2.32)were factors significantly associated with willingness to get vaccinated against Mpox. CONCLUSIONS Despite the ongoing outbreak within the continent, only a low proportion of surveyed health professionals expressed willingness to receive the Mpox vaccine. In addressing the outbreak, it is crucial to consider various factors such as recent travel to Mpox-affected countries, attitude towards Mpox, knowledge about the disease, and prior exposure to confirmed COVID-19 cases when developing and distributing information about Mpox vaccine. Consequently, substantial efforts must be directed towards educating and empowering health professionals in Ethiopia to effectively contribute to prevention and control measures.
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Affiliation(s)
- Getahun Fetensa
- Department of Nursing, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia; Department of Health, Behavior, and Society, Institute of Health, Jimma University, Jimma, Ethiopia; Center for Evidence-synthesis, Support, and Development in Africa (CESDA), PLC, Addis Ababa, Ethiopia.
| | - Tadesse Tolossa
- Department of Public Health, Institutes of Health Sciences, Wollega University, Nekemte, Ethiopia; Deakin Health Economics, School of Health and Social Development, Institute for Health Transformation, Deakin University, Geelong 3220, Australia
| | - Marga Besho
- Department of Midwifery, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia
| | - Girma Yadesa
- Department of Nursing, College of medical and health Sciences, Dire Dawa University, Dire dawa, Ethiopia
| | - Jilcha Gugsa
- Oromia Physician Association, Addis Ababa, Ethiopia
| | - Derara Girma Tufa
- Public Health Department, College of Health Sciences, Salale University, Fiche, Ethiopia
| | - Feyiso Bati
- Department of Public Health, College of Medicine and Health Science, Dire Dawa University, Dire Dawa, Ethiopia
| | - Kitesa Biresa Duftu
- Department of Epidemiology, Faculty of Public Health, Institute of Health, Jimma University, Jimma, Ethiopia
| | - Bizuneh Wakuma
- Department of Nursing, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia
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Huang CY, Su SB, Chen KT. A review of epidemiology, diagnosis, and management of Mpox: The role of One Health. Glob Health Med 2025; 7:1-12. [PMID: 40026855 PMCID: PMC11866911 DOI: 10.35772/ghm.2024.01072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/11/2024] [Accepted: 12/30/2024] [Indexed: 03/05/2025]
Abstract
Human monkeypox (Mpox) is an emerging zoonotic disease. Its clinical features are similar to but less severe than those of smallpox. The etiology of this disease is the monkeypox virus. This virus is a double-stranded DNA virus that is classified into the genus Orthopoxvirus and the family Poxviridae. Human monkeypox was first identified in 1970 and mainly occurred in Central and Western Africa. In 2022, outbreaks of Mpox virus infection occurred in several non-endemic countries and caused a potential threat to humans. It is urgent to take immediate action to control and prevent the outbreak of the Mpox virus infection. This paper summarizes the current status of Mpox and generated strategies for managing the Mpox epidemic. Although progress in the diagnostic methods and treatment of Mpox produces better knowledge, we argue that the sensitive surveillance for animal and human Mpox virus infection and evidence-based response and management of Mpox outbreaks is critical. This study highlights the need for further research on preventive and control strategies for Mpox disease approached through the One Health concept.
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Affiliation(s)
- Chien-Yuan Huang
- Division of Occupational Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Shih-Bin Su
- Department of Occupational Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Kow-Tong Chen
- Department of Occupational Medicine, Tainan Municipal Hospital (managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Yousaf MA, Michel M, Khan ATA, Noreen M, Bano S. Repurposing doxycycline for the inhibition of monkeypox virus DNA polymerase: a comprehensive computational study. In Silico Pharmacol 2025; 13:27. [PMID: 39958784 PMCID: PMC11825436 DOI: 10.1007/s40203-025-00307-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 01/17/2025] [Indexed: 02/18/2025] Open
Abstract
The global spread of monkeypox, caused by the double-stranded DNA monkeypox virus (MPXV), has underscored the urgent need for effective antiviral treatments. In this study, we aim to identify a potent inhibitor for MPXV DNA polymerase (DNAP), a critical enzyme in the virus replication process. Using a computational drug repurposing approach, we performed a virtual screening of 1615 FDA-approved drugs based on drug-likeness and molecular docking against DNAP. Among these, 1430 compounds met Lipinski's rule of five for drug-likeness, with Doxycycline emerging as the most promising competitive inhibitor, binding strongly to the DNAP active site with a binding affinity of - 9.3 kcal/mol. This interaction involved significant hydrogen bonds, electrostatic interactions, and hydrophobic contacts, with Doxycycline demonstrating a stronger affinity than established antivirals for smallpox, including Cidofovir, Brincidofovir, and Tecovirimat. Stability and flexibility analyses through a 200 ns molecular dynamics simulation and normal mode analysis confirmed the robustness of Doxycycline binding to DNAP. Overall, our results suggest Doxycycline as a promising candidate for monkeypox treatment, though additional experimental and clinical studies are needed to confirm its therapeutic potential and clinical utility. Supplementary Information The online version contains supplementary material available at 10.1007/s40203-025-00307-7.
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Affiliation(s)
- Muhammad Abrar Yousaf
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
| | - Maurice Michel
- Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
| | - Abeedha Tu-Allah Khan
- School of Biological Sciences, Faculty of Life-Sciences, University of the Punjab, Lahore, Pakistan
- Department of Biological Sciences, Faculty of Allied Health Sciences, Superior University, Lahore, Pakistan
| | - Misbah Noreen
- Department of Biological Sciences, Virtual University of Pakistan, Lahore, Pakistan
- Department of Wildlife and Ecology, University of Veterinary and Animal Sciences, Ravi Campus, Pattoki, Pakistan
| | - Saddia Bano
- Department of Biological Sciences, Virtual University of Pakistan, Lahore, Pakistan
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Zhu J, Jia X, Ren S, Zhang Z, Li H, Wang J, Song B, Wu W, Peng C. Inhibition of Polo-Like Kinase 1 Dampens the Replication of Vaccinia Virus in Mammalian Cells. J Med Virol 2025; 97:e70240. [PMID: 39953955 DOI: 10.1002/jmv.70240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 02/05/2025] [Accepted: 02/06/2025] [Indexed: 02/17/2025]
Abstract
Since the eradication of smallpox, zoonotic poxviruses, such as the mpox virus (MPXV), continue to pose a threat to public health. Identifying drugs that reduce poxvirus infection and replication, as well as understanding their molecular mechanisms, is essential for epidemic control. Polo-like kinase 1 (PLK1) has been shown to facilitate vaccinia virus (VACV) infection and replication. This study confirms the effects of the PLK1 inhibitors HMN-214 and ON-01910 on VACV replication in A549 cells. Both viral titers and DNA loads were significantly reduced in treated cells after infection. Additionally, ON-01910 demonstrated broad-spectrum antiviral activity against the lumpy skin disease virus (LSDV) and the infectious bovine rhinotracheitis virus (IBRV) in vitro. PLK1 knockdown in A549 cells also led to a reduction in VACV protein expression, viral titers, and DNA levels. Further analysis showed that VACV infection leads to the accumulation of PLK1 near viral factories. However, despite its strong in vitro effects, ON-01910 did not significantly reduce VACV replication in mice. These findings highlight the critical role of PLK1 in VACV replication and its potential as a target for antiviral therapy against orthopoxviruses.
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Affiliation(s)
- Junda Zhu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Xuejiao Jia
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Shuning Ren
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Zihui Zhang
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Hua Li
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Jing Wang
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Baifen Song
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Wenxue Wu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Chen Peng
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
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Ganesan A, Arunagiri T, Mani S, Kumaran VR, Sk G, Elumalai S, Kannaiah KP, Chanduluru HK. Mpox treatment evolution: past milestones, present advances, and future directions. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1057-1080. [PMID: 39225831 DOI: 10.1007/s00210-024-03385-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
An underestimated worldwide health concern, Monkeypox (Mpox) is becoming a bigger menace to the world's population. After smallpox was eradicated in 1970, Mpox was found in a rural region of Africa and quickly spread to other African countries. The etiological agent of the Mpox infection, the Mpox virus, is constantly evolving, and its capability for cross-species transmission led to a global outbreak in 2022 which led to several deaths throughout the world. This review aims to showcase the progressive treatment methods and emerging innovations in the diagnostic and prevention strategies for controlling Mpox. The clinical trial data for antiviral drugs were systematically collected and analyzed using statistical tests to determine the most effective antiviral treatment. Emerging viral protein inhibitors that are under investigation for Mpox treatment were also scrutinized in this review. Additionally, modern diagnostic methods, such as the Streamlined CRISPR On Pod Evaluation platform (SCOPE) and graphene quantum rods were reviewed, and the efficacy of mRNA vaccines with traditional smallpox vaccines used for Mpox were compared. The statistical analysis revealed that tecovirimat (TCV) is the most effective antiviral drug among the other evaluated drugs, showing superior efficacy in clinical trials. Similarly, mRNA vaccines offer greater effectiveness compared to conventional smallpox vaccines. Furthermore, emerging nanomedicine and herbal drug candidates were highlighted as potential future treatments for Mpox. The findings underscore the effectiveness of TCV in treating Mpox and highlight significant advancements in preventive treatments. The review also points to innovative approaches in vaccine technology and potential future therapies, including nanomedicine and herbal remedies, which may enhance Mpox management.
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Affiliation(s)
- Alagammai Ganesan
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India
| | - Thirumalai Arunagiri
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India
| | - Suganandhini Mani
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India
| | - Vamsi Ravi Kumaran
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India
| | - Gayathrii Sk
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India
| | - Sandhiya Elumalai
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India
| | - Kanaka Parvathi Kannaiah
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
| | - Hemanth Kumar Chanduluru
- SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
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Chen Z, Jiang Y, Cui J, Li W, Han W, Liu G. Elucidating the Mechanism of VVTT Infection Through Machine Learning and Transcriptome Analysis. Int J Mol Sci 2025; 26:1203. [PMID: 39940969 PMCID: PMC11818747 DOI: 10.3390/ijms26031203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/23/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
The vaccinia virus (VV) is extensively utilized as a vaccine vector in the treatment of various infectious diseases, cardiovascular diseases, immunodeficiencies, and cancers. The vaccinia virus Tiantan strain (VVTT) has been instrumental as an irreplaceable vaccine strain in the eradication of smallpox in China; however, it still presents significant adverse toxic effects. After the WHO recommended that routine smallpox vaccination be discontinued, the Chinese government stopped the national smallpox vaccination program in 1981. The outbreak of monkeypox in 2022 has focused people's attention on the Orthopoxvirus. However, there are limited reports on the safety and toxic side effects of VVTT. In this study, we employed a combination of transcriptomic analysis and machine learning-based feature selection to identify key genes implicated in the VVTT infection process. We utilized four machine learning algorithms, including random forest (RF), minimum redundancy maximum relevance (MRMR), eXtreme Gradient Boosting (XGB), and least absolute shrinkage and selection operator cross-validation (LASSOCV), for feature selection. Among these, XGB was found to be the most effective and was used for further screening, resulting in an optimal model with an ROC curve of 0.98. Our analysis revealed the involvement of pathways such as spinocerebellar ataxia and the p53 signaling pathway. Additionally, we identified three critical targets during VVTT infection-ARC, JUNB, and EGR2-and further validated these targets using qPCR. Our research elucidates the mechanism by which VVTT infects cells, enhancing our understanding of the smallpox vaccine. This knowledge not only facilitates the development of new and more effective vaccines but also contributes to a deeper comprehension of viral pathogenesis. By advancing our understanding of the molecular mechanisms underlying VVTT infection, this study lays the foundation for the further development of VVTT. Such insights are crucial for strengthening global health security and ensuring a resilient response to future pandemics.
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Affiliation(s)
- Zhili Chen
- Academy of Military Medical Sciences, Beijing 100850, China
| | - Yongxin Jiang
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun 130012, China (W.H.)
| | - Jiazhen Cui
- Academy of Military Medical Sciences, Beijing 100850, China
| | - Wannan Li
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun 130012, China (W.H.)
| | - Weiwei Han
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun 130012, China (W.H.)
| | - Gang Liu
- Academy of Military Medical Sciences, Beijing 100850, China
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11
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Wu J, Guo D. Systematic analysis of traditional Chinese medicine prescriptions provides new insights into drug combination therapy for pox. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118842. [PMID: 39306210 DOI: 10.1016/j.jep.2024.118842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 08/09/2024] [Accepted: 09/17/2024] [Indexed: 09/28/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The decline in cross-protection provided by the smallpox vaccine increases the risk of infection from other poxviruses. While drug combinations are a promising management, they remain underdeveloped for poxviruses. Prior to the development of the smallpox vaccine, China had long relied on herbal medicine to combat pox and accumulated a wealth of knowledge regarding different herb combinations and symptoms related to pox. The information was documented in the form of prescriptions. AIM OF THE STUDY The extensive data of prescriptions offer the potential for uncovering commonalities underlying these prescriptions, thereby providing valuable insights into the development of drug combinations against pox. MATERIALS AND METHODS The 2344 prescriptions were collected from the LTM-TCM database and 12 traditional Chinese medicine books. Firstly, the relative frequency of citation was utilized to identify the most used herbs among these prescriptions. TCMSP and LTM-TCM databases were employed to gather information about active compounds and their targets. GeneCards and DisGeNET databases were utilized to determine the associated targets for smallpox, cowpox, chickenpox, and mpox. Subsequently, network pharmacology analysis was conducted to investigate potential pathway information related to the most used herbs. A comparison of active compounds from these herbs resulted in the identification of 29 high-frequency compounds. The functions of these compounds were elucidated through gene overlap analysis, docking, and literature review. Finally, we summarized pox-related symptoms and used fidelity levels to distinguish specific herbs for corresponding symptoms. RESULTS Based on 2344 traditional pox-related prescriptions, we identified 19 most used herbs and 64 associated bio-functional modules for poxvirus treatment, with the most significant one being immunoregulation primarily involving CD4+ regulation. We also identified 29 leads that possess anti-inflammatory, antimicrobial, and antiviral properties. These herbs and leads hold the potential for pox treatment. Additionally, docking analysis suggested that these leads could inhibit poxvirus DNA synthesis, RNA capping machinery processes, and mature poxvirus particle formation, as well as immunosuppressors. The clinical features of mpox in 2022 were found to align well with our description of symptoms related to the pox. CONCLUSION Through the analysis of 2344 prescriptions for pox treatment, we obtained a comprehensive library of the most used herbs and high-frequency compounds, along with their potential functional spectrum. These libraries served as raw resources for drug combination development, while the identified symptom patterns and specific herbs greatly enhanced our insight into diverse treatments for pox patients.
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Affiliation(s)
- Jiawei Wu
- State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Dianjing Guo
- State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
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12
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Dutta S, Ghosh R, Dasgupta I, Sikdar P, Santra P, Maity D, Pritam M, Lee SG. Monkeypox: A comprehensive review on mutation, transmission, pathophysiology, and therapeutics. Int Immunopharmacol 2025; 146:113813. [PMID: 39674002 DOI: 10.1016/j.intimp.2024.113813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/13/2024] [Accepted: 12/04/2024] [Indexed: 12/16/2024]
Abstract
Monkeypox virus (MPXV) is the causative agent of the monkeypox (Mpox) disease, belongs to the Orthopoxvirus genus of the Poxviridae family. Due to the recent re-emergence of Mpox in 2024, this is the second time when the World Health Organization (WHO) declared Mpox as a Public Health Emergency of International Concern (PHEIC). This review intends to offer an in-depth analysis of Mpox, including its key characteristics, epidemiological, mutation, pathophysiology, transmission, and therapeutics. The infection of MPXV is a lethal threat to children, pregnant women, and immunocompromised individuals. However, we can prevent the infection by proper precautions including hygiene practices and minimizing exposure to infected individuals or animals. Multivalent mRNA vaccines, antibody-based immunotherapy, and combination drug therapies have all shown significant effectiveness in treating Mpox infection. In addition to addressing antivirals and drug resistance, the review also explores potential targets for vaccine and drug development, as well as the use of animal models for studying MPXV. Because of multiple mutational events, Mpox began exhibiting drug resistance. Overall, this review will contribute significantly to advancing the development of new vaccines and drug options for combating emerging Mpox.
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Affiliation(s)
- Somenath Dutta
- School of Chemical and Biomolecular Engineering, Pusan National University, Busan, South Korea; Department of Bioinformatics, Pondicherry Central University, Puducherry, India
| | - Rohan Ghosh
- Department of Bioinformatics, Pondicherry Central University, Puducherry, India; Department of Biotechnology, Konkuk University, Seoul, South Korea
| | - Ishita Dasgupta
- Department of Bioinformatics, Pondicherry Central University, Puducherry, India; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, United Kingdom
| | - Purbita Sikdar
- Department of Bioinformatics, Pondicherry Central University, Puducherry, India
| | - Priyasa Santra
- Department of Bioinformatics, Pondicherry Central University, Puducherry, India
| | - Debjit Maity
- School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Manisha Pritam
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow 226028, India; Laboratory of Malaria Immunology and Vaccinology, NIAID, NIH, Bethesda, MD 20892, United States.
| | - Sun Gu Lee
- School of Chemical and Biomolecular Engineering, Pusan National University, Busan, South Korea.
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Shafaati M, Forghani S, Shahsavand Davoudi A, Samiee R, Mohammadi K, Akbarpour S, Seifi A, Salehi M, Zare M. Current advances and challenges in mpox vaccine development: a global landscape. Ther Adv Vaccines Immunother 2025; 13:25151355251314339. [PMID: 39872308 PMCID: PMC11770767 DOI: 10.1177/25151355251314339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 12/16/2024] [Indexed: 01/30/2025] Open
Abstract
Given the surge in mpox outbreaks in 2022 and the advancements in domestic and international vaccine research, the effectiveness of smallpox vaccines in providing cross-protection against mpox remains crucial. Having learned from the COVID-19 pandemic, it is significant to continue evaluating existing vaccines to ensure their safety and efficacy. Developing new vaccines for widespread use against mpox and its emerging strains also serves as a preventive strategy in the ongoing battle against this dynamic infection. Here's an opportunity to control human-to-human transmission, give short deadlines, and avoid vaccine disparity. Public health systems must take decisive action to prevent the global spread of mpox, particularly among vulnerable groups. This action should include strengthening global surveillance, improving vaccine access, and ensuring equitable distribution, particularly in resource-poor settings, to prevent future outbreaks. This review aims to assess recent advancements and barriers in mpox vaccine development, emphasizing cross-protection and equitable vaccine distribution in resource-poor settings.
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Affiliation(s)
- Maryam Shafaati
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Shayan Forghani
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Reza Samiee
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Keyhan Mohammadi
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Akbarpour
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Seifi
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Salehi
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Zare
- Virology Department of Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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14
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Wei L, Wu Y, Li S, Weng J, Geng M, Mei M, Wei Z. In vitro enzyme characterization and several inhibitors for monkeypox virus core protease I7L. FEMS Microbiol Lett 2025; 372:fnaf008. [PMID: 39824654 DOI: 10.1093/femsle/fnaf008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 12/23/2024] [Accepted: 01/16/2025] [Indexed: 01/20/2025] Open
Abstract
Monkeypox is a zoonotic viral disease caused by the monkeypox virus, a member of the genus Orthopoxvirus within the family Poxviridae, which also includes the variola virus. On 14 August 2024, WHO Director-General declared monkeypox outbreak a public health emergency of international concern. Similar to variola virus core protease K7L, I7L could be identified as a promising target to fight against monkeypox virus. Our work provides a solid foundation as well as specific molecular tools (protease production methods, assay design, inhibitor design) that can now be used to probe the function of I7L in vitro. Notably, in this work, various reported covalent lead compounds for COVID-19 proteases were screened and A68, shikonin, and myricetin were identified as exhibiting high inhibitory activity against I7L. This work not only sheds light on effective inhibitors for the monkeypox virus core protease but also contributes to the broader search for antiviral agents targeting this enzyme.
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Affiliation(s)
- Lin Wei
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China
- Hubei Jiangxia Laboratory, Wuhan 430207, China
| | - Yuqi Wu
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China
| | - Shuai Li
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China
| | - Jun Weng
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Miaomiao Geng
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China
| | - Meng Mei
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China
- Hubei Jiangxia Laboratory, Wuhan 430207, China
| | - Zigong Wei
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan 430062, China
- Hubei Jiangxia Laboratory, Wuhan 430207, China
- National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Life Sciences, Hubei University, Wuhan 430062, China
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15
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Eslamkhah S, Aslan ES, Yavas C, Akcalı N, Batur LK, Abuaisha A, Yildirim EE, Solak M, White KN. Mpox virus (MPXV): comprehensive analysis of pandemic risks, pathophysiology, treatments, and mRNA vaccine development. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-024-03649-9. [PMID: 39777535 DOI: 10.1007/s00210-024-03649-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 11/18/2024] [Indexed: 01/11/2025]
Abstract
Mpox, formerly known as monkeypox, is a zoonotic disease caused by the Mpox virus (MPXV), which has recently attracted global attention due to its potential for widespread outbreaks. Initially identified in 1958, MPXV primarily spreads to humans through contact with infected wild animals, particularly rodents. Historically confined to Africa, the virus has expanded beyond endemic regions, with notable outbreaks in Europe and North America in 2022, especially among men who have sex with men (MSM). The World Health Organization (WHO) has declared the current Mpox outbreak a Public Health Emergency of International Concern. This review explores the epidemiology, pathophysiology, and clinical manifestations of MPXV, along with current treatment strategies and the role of mRNA vaccines. It emphasizes the importance of understanding the changing dynamics of Mpox transmission, which are influenced by factors such as waning immunity from smallpox vaccinations and increased global interconnectedness. The potential for developing multi-epitope vaccines that can stimulate robust immune responses is highlighted, showcasing how bioinformatics can facilitate the identification of immunogenic antigens. Continued research and investment in vaccine development are crucial to address the urgent need for effective candidates that can protect at-risk populations. In summary, this review underscores the necessity for proactive public health measures and collaborative efforts among healthcare authorities, researchers, and communities to mitigate the impact of Mpox and enhance global preparedness for future outbreaks.
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Affiliation(s)
- Sajjad Eslamkhah
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, 34015, Turkey
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey
| | - Elif Sibel Aslan
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, 34015, Turkey
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey
| | - Cuneyd Yavas
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, 34015, Turkey
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey
| | - Nermin Akcalı
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, 34015, Turkey
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey
| | - Lutfiye Karcıoglu Batur
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, 34015, Turkey
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey
| | - Asmaa Abuaisha
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey
| | - Erva Esma Yildirim
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, 34015, Turkey
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey
| | - Mustafa Solak
- Biruni University Research Center (B@MER), Biruni University, Istanbul, 34015, Turkey.
- Department of Medical Genetics, Faculty of Medicine, Biruni University, Merkezefendi Mahallesi G/75 Sk. No: 1-13, Zeytinburnu, Istanbul, 34010, Turkey.
| | - Kenneth N White
- School of Human Sciences, London Metropolitan University, London, UK
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16
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Chen C, Chen Y, Ye Z, Ali A, Yao S. Bioactive Deep Eutectic Solvent-Involved Sprayable Versatile Hydrogel for Monkeypox Virus Lesions Treatment. ACS APPLIED MATERIALS & INTERFACES 2025; 17:2148-2168. [PMID: 39727382 DOI: 10.1021/acsami.4c14905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
To address the issues of infectious virus, bacterial secondary infections, skin pigmentation, and scarring caused by monkeypox virus (MPXV), a sprayable hydrogel with versatile functions was developed with comprehensive properties. Based on current research, the bioactive deep eutectic solvent (DES) of rosmarinic acid-proanthocyanidin-glycol (RPG) was designed and synthesized as active agent, and molecular docking was applied to discover its binding to MPXV proteins through H-bonds and van der Waals interactions, and the docking results show the binding energies between RA, PC, Gly and MPXV proteins are -58.7188, -50.2311, and -18.4755 kcal/mol, respectively. Additionally, poly(vinyl alcohol) (PVA), borate, and xylitol (Xyl) were integrated with RPG to prepare the PB-RPG-Xyl hydrogel, which was characterized by popular ways. The pH-responsive properties of the hydrogel accelerated the release of RPG under acidic conditions, resulting in an increased cumulative release percentage of 84.83% at pH 5.5 at 210 min. Besides that, it was proved to have the expected sprayability, self-healing, adhesion, and shape-adaptability. The results of molecular dynamic simulation were meaningful to understanding its formation and self-healing mechanisms. Furthermore, the hydrogel shows ideal degradability, removability, and biocompatibility. Lastly, its multiple functions were systematically explored, including UV-blocking, blood clotting, cooling, antioxidant, antibacterial, and virus inhibition properties. The developed sprayable PB-RPG-Xyl hydrogel represents the first promising dressing based on natural bioactive DES for MPXV lesions management, which not only expands the application of green solvents in health care but also provides a convenient and effective treatment process for MPXV infection in the face of difficult skin lesions and complex treatment needs.
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Affiliation(s)
- Chen Chen
- School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Yu Chen
- South Sichuan Institute of Translational Medicine, College of Pharmacy, Southwest Medical University, Luzhou, 646000, China
| | - Zhiyi Ye
- School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Ahmad Ali
- School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Shun Yao
- School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
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17
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Linani A, Benarous K, Erol E, Bou-Salah L, Serseg T, Yousfi M. In silico analysis of identified molecules using LC-HR/MS of Cupressus sempervirens L. ethyl acetate fraction against three monkeypox virus targets. J Biomol Struct Dyn 2025; 43:534-549. [PMID: 37982304 DOI: 10.1080/07391102.2023.2283149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 11/06/2023] [Indexed: 11/21/2023]
Abstract
Monkeypox virus is a viral disease transmitted to humans through contact with infected animals, such as monkeys and rodents, or through direct contact with the bodily fluids or lesions of infected humans. The aim of this study is to evaluate in silico the inhibition effect of eight Cupressus sempervirens L. ethyl acetate fraction identified molecules using LC-MS on three monkeypox targets such as the vaccinia virus thymidylate kinase (VTK), the viral profilin-like protein (VPP), and the viral RNA polymerase (VRP). The study consist of using molecular docking with AutoDock vina based on the lowest energy value in kcal/mol, pharmacokinetics prediction with pre-ADMET v2.0 server, and prediction of biological activity with the PASS server tool. The best complexes were subjected to molecular dynamics simulation (MD) study to confirm their stability using Desmond software. The used molecules were vitamin C, vanillic acid (Pol), Flav1 (Catechin), Flav2 (Epicatechin), Flav3 (Hyperoside), Flav4 (Luteolin), Flav5 (Taxifolin), and Flav6 (Quercetin). The results show that flavonoids are potent to VTK, VPP and effectively block the VRP channel with energy values ranging from -7.0 to -9.3 kcal/mol. Further, MD simulation supports Flav1 and, Flav2 for notable stability in the VTK binding pocket through hydrogen and hydrophobic interactions. PASS results predicted various biological activities with promising VTK and VRP inhibition activities. The studied molecules could constitute a safer alternative to current drugs, which often cause adverse side effects.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Abderahmane Linani
- Fundamental sciences laboratory, Amar Telidji University, Laghouat, Algeria
| | - Khedidja Benarous
- Fundamental sciences laboratory, Amar Telidji University, Laghouat, Algeria
| | - Ebru Erol
- Faculty of Pharmacy, Department of Analytical Chemistry, Bezmialem Vakif University, Istanbul, Türkiye
| | - Leila Bou-Salah
- Fundamental sciences laboratory, Amar Telidji University, Laghouat, Algeria
| | - Talia Serseg
- Fundamental sciences laboratory, Amar Telidji University, Laghouat, Algeria
- Laboratoire de sciences appliquées et didactiques, Ecole Normale Supérieure de Laghouat, Laghouat, Algeria
| | - Mohamed Yousfi
- Fundamental sciences laboratory, Amar Telidji University, Laghouat, Algeria
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18
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Chen L, Shang C, Wang Z, Zheng M, Zhang C, Li D, Yang Z, Dong Y, Xu Y, Yuan Y, Fan S, Zhong W, Lin J, Li X. Chemical cross-linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual-antigen subunit vaccine. MedComm (Beijing) 2025; 6:e70045. [PMID: 39781294 PMCID: PMC11707423 DOI: 10.1002/mco2.70045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 11/08/2024] [Accepted: 11/21/2024] [Indexed: 01/12/2025] Open
Abstract
Antigen uptake, processing, and presentation are crucial for the immune responses of protein-based vaccines. Herein, we introduced a reversible chemical cross-linking strategy to engineer protein antigens, which can be tracelessly removed upon antigen-presenting cell (APC) uptake and cellular reduction. The chemically cross-linked antigen proteins presented significantly enhanced uptake and epitope presentation by APC. We applied this strategy to monkeypox virus antigens A29L and A35R to construct dual-antigen subunit vaccines. Our results revealed that chemical cross-linking was robust enough to improve both proteins' APC uptake and lymph node accumulation, with each protein being chemically cross-linked and administered separately. In vivo validation revealed that the chemical cross-linking of the two antigen proteins improved immune responses, with increases in antigen-specific antibody and live virus-neutralizing antibody production. Monkeypox virus challenge experiments revealed that dual-antigen vaccines prepared via the chemical cross-linking strategy mitigated tissue damage, reduced the virus load, and extended mouse survival, which proved that the chemical cross-linking strategy is valuable for protein-based subunit vaccine development. In consideration of the current threats from the monkeypox virus and potential future emerging pathogens, the chemical cross-linking strategy provide powerful tools.
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Affiliation(s)
- Long Chen
- Department of PharmacyPeking University Third Hospital Cancer CenterPeking University Third HospitalBeijingChina
| | - Chao Shang
- Changchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchunChina
| | - Zihao Wang
- National Engineering Research Center for the Emergency DrugBeijing Institute of Pharmacology and ToxicologyBeijingChina
| | - Mengzhu Zheng
- Key Laboratory of Tropical Biological Resources of Ministry of EducationSong Li's Academician Workstation of Hainan UniversitySchool of Pharmaceutical SciencesHainan UniversityHaikouChina
| | - Cuiling Zhang
- Changchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchunChina
| | - Dapeng Li
- Changchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchunChina
| | - Zhanqun Yang
- Department of PharmacyPeking University Third Hospital Cancer CenterPeking University Third HospitalBeijingChina
| | - Yuchao Dong
- National Engineering Research Center for the Emergency DrugBeijing Institute of Pharmacology and ToxicologyBeijingChina
| | - Yuru Xu
- National Engineering Research Center for the Emergency DrugBeijing Institute of Pharmacology and ToxicologyBeijingChina
| | - Yunsheng Yuan
- Engineering Research Center of Cell & Therapeutic AntibodyMinistry of EducationShanghai Jiao Tong University School of PharmacyShanghaiChina
| | - Shiyong Fan
- National Engineering Research Center for the Emergency DrugBeijing Institute of Pharmacology and ToxicologyBeijingChina
| | - Wu Zhong
- National Engineering Research Center for the Emergency DrugBeijing Institute of Pharmacology and ToxicologyBeijingChina
| | - Jian Lin
- Department of PharmacyPeking University Third Hospital Cancer CenterPeking University Third HospitalBeijingChina
- Key Laboratory of Tropical Biological Resources of Ministry of EducationSong Li's Academician Workstation of Hainan UniversitySchool of Pharmaceutical SciencesHainan UniversityHaikouChina
| | - Xiao Li
- Changchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchunChina
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19
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Rizk Y, Lippi G, Henry BM, Notarte KI, Rizk JG. Update on Mpox Management: Epidemiology, Vaccines and Therapeutics, and Regulatory Changes. Drugs 2025; 85:1-9. [PMID: 39497022 DOI: 10.1007/s40265-024-02117-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2024] [Indexed: 11/06/2024]
Abstract
Mpox, caused by the monkeypox virus (MPXV), is categorized into two primary clades: Clade I and Clade II, with notable outbreaks linked to Clade IIb. Historically endemic in Africa, recent years have seen significant global spread. The World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern in August 2024, highlighting the emergence of Clade Ib outside Africa and the broadening demographic impact of the outbreak. This review updates the current status of mpox vaccines and treatments, including their safety and effectiveness. There are two US Food and Drug Administration (FDA)-approved vaccines for the prevention of mpox disease, JynneosTM and ACAM2000®. The JynneosTM vaccine, recommended for high-risk individuals, has seen limited uptake despite its efficacy in preventing disease. Tecovirimat, while FDA-approved for smallpox and available in the European Union for mpox, has shown mixed results in recent trials, with new data suggesting limited effectiveness in Clade I infections and emergence of new mutations with resistance to this drug. Brincidofovir and Vaccinia Immune Globulin Intravenous offer additional treatment options, particularly for severe cases, although their use is constrained by regulatory and logistical challenges. Furthermore, the WHO recently approved the first commercial molecular assay, the Alinity m MPXV assay by Abbott Molecular Inc., for emergency use-an essential step in expanding testing capacity in regions experiencing mpox outbreaks. These updates underscore the critical need for continued research to enhance therapeutic outcomes and adapt public health strategies. Ensuring equitable access to vaccines, treatments, and diagnostics remains a significant challenge as the global community responds to the evolving mpox situation.
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Affiliation(s)
- Youssef Rizk
- Division of Family Medicine, Department of Internal Medicine, Lebanese American University Gilbert and Rose-Marie Chagoury School of Medicine, Beirut, Lebanon
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University Hospital of Verona, Verona, Italy
| | - Brandon M Henry
- Clinical Laboratory, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Kin Israel Notarte
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - John G Rizk
- Department of Practice, Sciences, and Health Outcomes Research, University of Maryland School of Pharmacy, Baltimore, MD, 21201, USA.
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Singh V, Dwivedi S, Agrawal R, Sadashiv, Fatima G, Abidi A. The Human Monkeypox Virus and Host Immunity: Emerging Diagnostic and Therapeutic Challenges. Infect Disord Drug Targets 2025; 25:e18715265309361. [PMID: 39161149 DOI: 10.2174/0118715265309361240806064619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/04/2024] [Accepted: 06/25/2024] [Indexed: 08/21/2024]
Abstract
This article explores the Human Monkeypox Virus (MPV), a contagious virus that causes disease in both vertebrates and insects. It originated in Denmark in 1958 and expanded beyond Africa during the 1970s. The virus was initially detected in the United States in 2003 following the hospitalisation of a toddler who had been bitten by a prairie dog. The article examines the identification of the virus, its categorization into two genetic groups with different levels of harmfulness, and its genetic changes over time due to specific influences. Additionally, it investigates the immunological reaction to MPXV, encompassing both the innate and adaptive systems. This article also addresses the diagnostic difficulties presented by MPXV's resemblance to other orthopoxviruses and the progress made in molecular diagnostics. The paper analyses different therapeutic interventions, such as tecovirimat, an antiviral medication, and JYNNEOS, a vaccine, in terms of their efficacy, potential drawbacks, and the difficulties encountered in managing outbreaks. The future outlook emphasises the necessity of inventive research methodologies, worldwide monitoring, and individualised medical treatments to counteract the dissemination of MPXV and alleviate its consequences on public health.
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Affiliation(s)
- Vijay Singh
- Department of Biochemistry, All India Institute of Medical Sciences, Gorakhpur, 273008, India
| | - Shailendra Dwivedi
- Department of Biochemistry, All India Institute of Medical Sciences, Gorakhpur, 273008, India
| | - Ruchika Agrawal
- Department of ENT, All India Institute of Medical Sciences, Gorakhpur, 273008, India
| | - Sadashiv
- Department of Biochemistry, All India Institute of Medical Sciences, Raebareli, 229405, India
| | - Ghizal Fatima
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, India
| | - Afroz Abidi
- Department of Pharmacology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, India
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21
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Yang J, Qin G, Huang B, Song H, Sun J, Postings M, Scott P, Zhao C, Wang C, Tan W, Ren J, Qu X. Metallo-supramolecular complexes enantioselectively target monkeypox virus RNA G-quadruplex and bolster immune responses against MPXV. Natl Sci Rev 2025; 12:nwae388. [PMID: 39758126 PMCID: PMC11697978 DOI: 10.1093/nsr/nwae388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 09/26/2024] [Accepted: 10/07/2024] [Indexed: 01/07/2025] Open
Abstract
The Mpox virus (MPXV) has emerged as a formidable orthopoxvirus, posing an immense challenge to global public health. An understanding of the regulatory mechanisms of MPXV infection, replication and immune evasion will benefit the development of novel antiviral strategies. Despite the involvement of G-quadruplexes (G4s) in modulating the infection and replication processes of multiple viruses, their roles in the MPXV life cycle remain largely unknown. Here, we found a highly conservative and stable G4 in MPXV that acts as a positive regulatory element for viral immunodominant protein expression. Furthermore, by screening 42 optically pure chiral metal complexes, we identified the Λ enantiomer of a pair of chiral helical compounds that can selectively target mRNA G4 and enhance expression of the 39-kDa core protein encoded by the MPXV A5L gene. Mechanistically, RNA G4-specific helicase DHX36 inhibits A5L protein expression by unwinding G4s. In contrast, MH3 Λ enhanced mRNA stability by specifically targeting G4 structures and subsequently increased protein expression. Furthermore, given the pivotal role of the 39-kDa core protein in activating immune responses and facilitating virion maturation, modulation of MPXV G4 folding by MH3 Λ exhibited inhibitory effects on MPXV replication through enhancing the immune response. Our findings underscore the critical involvement of G4 in the MPXV life cycle and offer potential avenues for developing antiviral drugs that target G4.
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Affiliation(s)
- Jie Yang
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Geng Qin
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Baoying Huang
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), Beijing 102206, China
| | - Hualong Song
- Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
| | - Jiewei Sun
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), Beijing 102206, China
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Miles Postings
- Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
| | - Peter Scott
- Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
| | - Chuanqi Zhao
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Chunyu Wang
- State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun 130012, China
| | - Wenjie Tan
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), Beijing 102206, China
| | - Jinsong Ren
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Xiaogang Qu
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
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Banna MHA, Seidu AA, Mallick T, Rahman N, Sultana MS, Mouly HA, Alshahrani NZ, Akter N, Mahmud T, Hossain S, Sheikh A, Biswas A, Sahrin S, Hassan MN, Khan MSI. Knowledge regarding human monkeypox among a sample of undergraduate and post-graduate students from selected tertiary institutions in Bangladesh: An online-based cross-sectional study. PLoS One 2024; 19:e0315677. [PMID: 39739877 DOI: 10.1371/journal.pone.0315677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 11/28/2024] [Indexed: 01/02/2025] Open
Abstract
BACKGROUND The recent human monkeypox (mpox) outbreak in 2022 has become a serious concern due to its rapid expansion to various non-endemic countries. There is limited information about the knowledge regarding mpox among the Bangladeshi population. Therefore, this study's objectives were to: (i) determine the level of knowledge regarding mpox among undergraduate and post-graduate students in Bangladesh, and (ii) assess the determinants of knowledge regarding mpox among the study sample. METHODS An online-based cross-sectional study was conducted among 879 tertiary-level students from selected tertiary institutions (n = 13) in Bangladesh. The structured questionnaire consisted of two parts: (i) socio-demographic information and (ii) an assessment of knowledge regarding mpox. The Kruskal-Wallis test, Mann-Whitney test, and multivariable quantile regression model were employed. RESULTS The median age of the study participants was 23 years (IQR: 25-22). Low knowledge of mpox was found among study participants (20.7%, 23.2% and 56.1% had good, moderate and poor knowledge, respectively). The overall median knowledge score for mpox was 11 (IQR: 16-6). The median knowledge score of mpox significantly differed by participants' gender, study major, and academic education about mpox. In the quantile regression analysis, the association between gender and mpox knowledge was observed at the 25th (β = 1.343), 50th (β = 2.00) and 75th (β = 1.59) quantiles with females having more knowledge compared to males. The effects of study group were significant at 25th (β = 1.746), 50th (β = 1.5), 75th (β = 1.361) and 90th (β = 1.248) quantiles. Thus, those in medical or public health programs were likely to have more knowledge about mpox relative to those who were in non-medical related study groups. Students who received information about mpox during their education were more knowledgeable compared to those who had not, with statistical significance occurring at 10th (β = 3.711), 25th (β = 6.656), 50th (β = 5.75), 75th (β = 3.404) and 90th (β = 2.592) quantiles. CONCLUSION These findings imply that educational interventions about mpox should consider the gender dynamics and program of study among the students in Bangladesh.
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Affiliation(s)
- Md Hasan Al Banna
- Department of Food Microbiology, Faculty of Nutrition and Food Science, Patuakhali Science and Technology University, Patuakhali, Bangladesh
| | - Abdul-Aziz Seidu
- Public Health and Tropical Medicine, James Cook University, Townsville, Australia
| | - Trisha Mallick
- Department of Environmental Sanitation, Faculty of Nutrition and Food Science, Patuakhali Science and Technology University, Patuakhali, Bangladesh
| | - Nahidur Rahman
- Department of Food Processing and Engineering, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh
| | - Mst Sadia Sultana
- Department of Health, Society, & Behavior, UC Irvine Joe C. Wen School of Population & Public Health, Irvine, California, United States of America
| | | | - Najim Z Alshahrani
- Department of Family and Community Medicine, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Nargees Akter
- Department of Geography and Environmental Studies, University of Chittagong, Chittagong, Bangladesh
| | - Tareq Mahmud
- Department of Public Health and Informatics, Jahangirnagar University, Dhaka, Bangladesh
| | | | | | - Ashish Biswas
- Faculty of Agriculture, Patuakhali Science and Technology University, Patuakhali, Bangladesh
| | - Sumaia Sahrin
- Department of Human Nutrition and Dietetics, Faculty of Nutrition and Food Science, Patuakhali Science and Technology University, Patuakhali, Bangladesh
| | - Md Nazmul Hassan
- Department of Environmental Sanitation, Faculty of Nutrition and Food Science, Patuakhali Science and Technology University, Patuakhali, Bangladesh
| | - Md Shafiqul Islam Khan
- Department of Cellular and Molecular Biology, Faculty of Biotechnology and Genetic Engineering, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh
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23
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Ding J, Liu XC, Hong J, Zhang QM, Xu XW, Liu YQ, Yu CQ. Knowledge about, attitudes toward and acceptance and predictors of intention to receive the mpox vaccine among cancer patients in China: A cross-sectional survey. Hum Vaccin Immunother 2024; 20:2337157. [PMID: 38644633 PMCID: PMC11037286 DOI: 10.1080/21645515.2024.2337157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 03/27/2024] [Indexed: 04/23/2024] Open
Abstract
This study aimed to investigate the knowledge about, attitudes toward, and acceptance and predictors of receiving the mpox vaccine among Chinese cancer patients. Patients were selected using a convenience sampling method. A web-based self-report questionnaire was developed to assess cancer patients' knowledge, attitudes, and acceptance regarding the mpox vaccine. Multivariate logistic regression analysis was used to determine predictors of acceptance of the mpox vaccine. A total of 805 cancer patients were included in this study, with a vaccine hesitancy rate of 27.08%. Approximately 66% of the patients' information about mpox and the vaccine came from the mass media, and there was a significant bias in the hesitant group's knowledge about mpox and the vaccine. Multivariable logistic regression analysis suggested that retirement; chemotherapy; the belief that the mpox vaccine could prevent disease, that vaccination should be compulsory when appropriate and that the mpox vaccine prevents mpox and reduces complications; the willingness to pay for the mpox vaccine; the willingness to recommend that friends and family receive the mpox vaccine; and the belief that the mpox vaccine should be distributed fairly and equitably were factors that promoted vaccination. The belief that mpox worsens tumor prognosis was a driving factor for vaccine hesitancy. This study investigated the knowledge of cancer patients about mpox and the vaccine, evaluated the acceptance and hesitancy rates of the mpox vaccine and examined the predictors of vaccination intention. We suggest that the government scientifically promote the vaccine and develop policies such as free vaccination and personalized vaccination to increase the awareness and acceptance rate of the mpox vaccine.
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Affiliation(s)
- Jie Ding
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai, China
- TCM gynecology department, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Xing-Chen Liu
- Pathology department, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Jing Hong
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai, China
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Qing-Mei Zhang
- Anesthesiology department, Chaohu Hospital, Anhui Medical University, Hefei, Anhui Province, China
| | - Xiao-Wan Xu
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Yi-Qun Liu
- TCM gynecology department, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Chao-Qin Yu
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai, China
- TCM gynecology department, The First Affiliated Hospital of Naval Medical University, Shanghai, China
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24
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Yang X, Yang X, Jiang W, Luo N, Hu Y, Yang Y, Yang X, Hou L, Zhang J, Hu C, Lin J. A cross-sectional investigation of factors influencing mpox vaccine hesitancy for students in Southwest China. Hum Vaccin Immunother 2024; 20:2309704. [PMID: 38300140 PMCID: PMC10841021 DOI: 10.1080/21645515.2024.2309704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/21/2024] [Indexed: 02/02/2024] Open
Abstract
From July to September 2023, China reported over 1, 400 confirmed cases of mpox transmitted mainly through sexual contact between males. Meanwhile, the percentage of men who have sex with men at universities in southwestern China is increasing every year, which is likely to lead to a potential spread of mpox on campuses. Vaccination is an effective preventive measure against infectious diseases, this study examined the willingness of university students in Southwest China to receive the mpox vaccine and analyzed the factors influencing their decision. A cross-sectional survey was conducted among 7311 university students from 10 universities in Southwest China between August 13 and September 1, 2023. The survey revealed a hesitancy rate of 56.13% toward the mpox vaccine, with the most common reason being concerns about vaccine safety (1407/4104, 34.29%). Univariate analysis identified 13 variables that significantly differed between the vaccine acceptance and vaccine hesitancy groups. Multivariate logistic regression analyses indicated protective factors for vaccine hesitancy, such as sexually transmitted diseases, previous knowledge about mpox, frequent information about mpox, people can get reinfection of mpox, and worries about mpox endemic in China. Additionally, the confidence and convenience dimensions in the 3Cs model were identified as risk factors for mpox vaccine hesitancy. This study found a high rate of vaccine hesitancy among university students in Southwest China regarding the mpox vaccine. Collaboration between university and healthcare departments is recommended to address mpox vaccine hesitancy among college students, thereby promoting their willingness to receive the mpox vaccine.
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Affiliation(s)
- Xiu Yang
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Xuetao Yang
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Wenyi Jiang
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Na Luo
- Department of Operation Room, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Yibo Hu
- Department of Stomatology, School of Medicine, Nankai University, Tianjin, China
| | - Ya Yang
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Xidan Yang
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Lingli Hou
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Jingjing Zhang
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Congxia Hu
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
| | - Jihui Lin
- Wound Healing Basic Research and Clinical Application Key Laboratory of LuZhou, School of Nursing, Southwest Medical University, Luzhou, Sichuan, China
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25
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Kumar S, Guruparan D, Karuppanan K, Kumar KJS. Comprehensive Insights into Monkeypox (mpox): Recent Advances in Epidemiology, Diagnostic Approaches and Therapeutic Strategies. Pathogens 2024; 14:1. [PMID: 39860962 PMCID: PMC11768232 DOI: 10.3390/pathogens14010001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 12/23/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
Monkeypox (mpox) is a viral infection closely related to smallpox, manifesting as a milder febrile rash in affected individuals. Over the past two decades, the incidence of mpox has surged, possibly linked to a declining immunity against the smallpox vaccine worldwide. Recent outbreaks of mpox in multiple countries have sparked concerns regarding altered transmission patterns and the potential for a global menace. In this article, we present a multidimensional review encompassing the latest scientific discoveries, illuminating the intricate structure of the human mpox virus. Key findings include advancements in understanding the virus's molecular mechanisms, which highlight its genetic adaptability and potential for zoonotic spillover. Diagnostic innovations, such as improved molecular assays, have enhanced detection accuracy, while novel therapeutic strategies, including antiviral drugs and vaccines, show promise in mitigating outbreaks. Our conclusions emphasize the importance of robust surveillance systems, vaccination programs, and rapid response strategies to curb mpox's spread. Future recommendations include strengthening global collaboration for zoonotic disease surveillance, advancing the research on host-pathogen interactions, and developing next-generation therapeutics to address this emerging public health threat effectively.
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Affiliation(s)
- Suresh Kumar
- Faculty of Health and Life Sciences, Management and Science University, Shah Alam 40100, Malaysia; (S.K.); (D.G.)
| | - Dhanyashri Guruparan
- Faculty of Health and Life Sciences, Management and Science University, Shah Alam 40100, Malaysia; (S.K.); (D.G.)
| | - Kalimuthu Karuppanan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India;
| | - K. J. Senthil Kumar
- Center for General Education, National Chung Hsing University, Taichung 402, Taiwan
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26
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Avril A, Guillier S, Rasetti-Escargueil C. Development of Effective Medical Countermeasures Against the Main Biowarfare Agents: The Importance of Antibodies. Microorganisms 2024; 12:2622. [PMID: 39770824 PMCID: PMC11677989 DOI: 10.3390/microorganisms12122622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/05/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
The COVID-19 and mpox crisis has reminded the world of the potentially catastrophic consequences of biological agents. Aside from the natural risk, biological agents can also be weaponized or used for bioterrorism. Dissemination in a population or among livestock could be used to destabilize a nation by creating a climate of terror, by negatively impacting the economy and undermining institutions. The Centers for Disease Control and Prevention (CDC) classify biological agents into three categories (A or Tier 1, B and C) according to the risk they pose to the public and national security. Category A or Tier 1 consists of the six pathogens with the highest risk to the population (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox and viral hemorrhagic fevers). Several medical countermeasures, such as vaccines, antibodies and chemical drugs, have been developed to prevent or cure the diseases induced by these pathogens. This review presents an overview of the primary medical countermeasures, and in particular, of the antibodies available against the six pathogens on the CDC's Tier 1 agents list, as well as against ricin.
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Affiliation(s)
- Arnaud Avril
- Unité Interaction Hôte-Pathogène, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 91220 Brétigny-sur-Orge, France
| | - Sophie Guillier
- Unité Bactériologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 91220 Brétigny-sur-Orge, France;
- UMR_MD1, Inserm U1261, 91220 Brétigny sur Orge, France
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27
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Duan H, Shi Q, Yue X, Zhang Z, Liu L, Wang Y, Cao Y, Ou Z, Liang L, Hu J, Shi H. Identification of core therapeutic targets for Monkeypox virus and repurposing potential of drugs: A WEB prediction approach. PLoS One 2024; 19:e0303501. [PMID: 39642129 PMCID: PMC11623562 DOI: 10.1371/journal.pone.0303501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 10/03/2024] [Indexed: 12/08/2024] Open
Abstract
A new round of monkeypox virus has emerged in the United Kingdom since July 2022 and rapidly swept the world. Currently, despite numerous research groups are studying this virus and seeking effective treatments, the information on the open reading frame, inhibitors, and potential targets of monkeypox has not been updated in time, and the comprehension of monkeypox target ligand interactions remains a key challenge. Here, we first summarized and improved the open reading frame information of monkeypox, constructed the monkeypox inhibitor library and potential targets library by database research as well as literature search, combined with advanced protein modeling technologies (Sequence-based and AI algorithms-based homology modeling). In addition, we build monkeypox virus Docking Server, a web server to predict the binding mode between targets and substrate. The open reading frame information, monkeypox inhibitor library, and monkeypox potential targets library are used as the initial files for server docking, providing free interactive tools for predicting ligand interactions of monkeypox targets, potential drug screening, and potential targets search. In addition, the update of the three databases can also effectively promote the study of monkeypox drug inhibition mechanism and provide theoretical guidance for the development of drugs for monkeypox.
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Affiliation(s)
- Huaichuan Duan
- Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Quanshan Shi
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Xinru Yue
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Zelan Zhang
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Ling Liu
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Yueteng Wang
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Yujie Cao
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Zuoxin Ou
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Li Liang
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Jianping Hu
- Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, China
| | - Hubing Shi
- Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
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28
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Huo S, Wu L, Huang B, Liu N, Sun J, Ye F, Deng Y, Chen J, Gong L, Zhu W, Xu Z, Tan W. Identification of the VP37 pocket of monkeypox virus as a promising target for pan-orthopoxvirus inhibitors through virtual screening and antiviral assays. Emerg Microbes Infect 2024; 13:2373309. [PMID: 38922308 PMCID: PMC11251428 DOI: 10.1080/22221751.2024.2373309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 06/22/2024] [Indexed: 06/27/2024]
Affiliation(s)
- Shuting Huo
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
| | - Leyun Wu
- State Key Laboratory of Drug Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Baoying Huang
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
| | - Nan Liu
- Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Jiewei Sun
- School of Pharmacy, Xinxiang Medical University, Xinxiang, People’s Republic of China
| | - Fei Ye
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
| | - Yao Deng
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
| | - Jing Chen
- Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Likun Gong
- Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Weiliang Zhu
- State Key Laboratory of Drug Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Zhijian Xu
- State Key Laboratory of Drug Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Wenjie Tan
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
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Sun H, Miao Y, Yang X, Guo L, Li Q, Wang J, Long J, Zhang Z, Shi J, Li J, Cao Y, Yu C, Mai J, Rong Z, Feng J, Wang S, Yang J, Wang S. Rapid identification of A29L antibodies based on mRNA immunization and high-throughput single B cell sequencing to detect Monkeypox virus. Emerg Microbes Infect 2024; 13:2332665. [PMID: 38517731 PMCID: PMC10984235 DOI: 10.1080/22221751.2024.2332665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 03/15/2024] [Indexed: 03/24/2024]
Abstract
With the large number of atypical cases in the mpox outbreak, which was classified as a global health emergency by the World Health Organization (WHO) on 23 July 2022, rapid diagnosis of mpox and diseases with similar symptoms to mpox such as chickenpox and respiratory infectious diseases in the early stages of viral infection is key to controlling the spread of the outbreak. In this study, antibodies against the monkeypox virus A29L protein were efficiently and rapidly identified by combining rapid mRNA immunization with high-throughput sequencing of individual B cells. We obtained eight antibodies with a high affinity for A29L validated by ELISA, which were was used as the basis for developing an ultrasensitive fluorescent immunochromatographic assay based on multilayer quantum dot nanobeads (SiTQD-ICA). The SiTQD-ICA biosensor utilizing M53 and M78 antibodies showed high sensitivity and stability of detection: A29L was detected within 20 min, with a minimum detection limit of 5 pg/mL. A specificity test showed that the method was non-cross-reactive with chickenpox or common respiratory pathogens and can be used for early and rapid diagnosis of monkeypox virus infection by antigen detection. This antibody identification method can also be used for rapid acquisition of monoclonal antibodies in early outbreaks of other infectious diseases for various studies.
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Affiliation(s)
- Huisheng Sun
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Yiqi Miao
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Xingsheng Yang
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Liang Guo
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Qingyu Li
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Jing Wang
- Beijing Institute of Pharmacology and Toxicology, Beijing, People's Republic of China
| | - Jinrong Long
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Zhen Zhang
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Jingqi Shi
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Jian Li
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Yiming Cao
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Changxiao Yu
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Jierui Mai
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Zhen Rong
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Jiannan Feng
- Beijing Institute of Pharmacology and Toxicology, Beijing, People's Republic of China
| | - Shumei Wang
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Jing Yang
- Bioinformatics center of AMMS, Beijing, People's Republic of China
| | - Shengqi Wang
- Bioinformatics center of AMMS, Beijing, People's Republic of China
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de Oliveira Neto NF, Caixeta RAV, Zerbinati RM, Zarpellon AC, Caetano MW, Pallos D, Junges R, Costa ALF, Aitken-Saavedra J, Giannecchini S, Braz-Silva PH. The Emergence of Saliva as a Diagnostic and Prognostic Tool for Viral Infections. Viruses 2024; 16:1759. [PMID: 39599873 PMCID: PMC11599014 DOI: 10.3390/v16111759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 11/06/2024] [Accepted: 11/07/2024] [Indexed: 11/29/2024] Open
Abstract
Saliva has emerged as a promising diagnostic fluid for viral infections, enabling the direct analysis of viral genetic material and the detection of infection markers such as proteins, metabolites, microRNAs, and immunoglobulins. This comprehensive review aimed to explore the use of saliva as a diagnostic tool for viral infections, emphasizing its advantages and limitations. Saliva stands out due to its simplicity and safety in collection, along with the convenience of self-collection without the need for healthcare supervision, while potentially being comparable to urine and blood in terms of effectiveness. Herein, we highlighted the significant potential of saliva in assessing viral loads and diagnosing viral infections, such as herpesviruses, HPV, PyV, TTV, SARS-CoV-2, and MPXV. The detection of viral shedding in saliva underscores its utility in early diagnosis, the monitoring of infection progression, and evaluating treatment responses. The non-invasive nature of saliva collection makes it an appealing alternative to more invasive methods, promoting better patient compliance and facilitating large-scale screening and surveillance. As such, we further highlight current evidence on the use of saliva as a prognostic tool. Although a significant amount of data is already available, further investigations are warranted to more comprehensively assess the added benefit from the utilization of salivary biomarkers in the clinics. Salivary biomarkers show great promise for the early detection and prevention of viral infection complications, potentially improving disease management and control at the population level. Integrating these non-invasive tools into routine clinical practice could enhance personalized healthcare strategies and patient outcomes. Future studies should focus on establishing standardization protocols, validating the accuracy of salivary diagnostics, and expanding clinical research to enhance the diagnostic and monitoring capabilities of salivary biomarkers.
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Affiliation(s)
- Nilson Ferreira de Oliveira Neto
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo 05508-000, Brazil; (N.F.d.O.N.); (R.A.V.C.); (A.C.Z.); (M.W.C.)
| | - Rafael Antônio Velôso Caixeta
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo 05508-000, Brazil; (N.F.d.O.N.); (R.A.V.C.); (A.C.Z.); (M.W.C.)
| | - Rodrigo Melim Zerbinati
- Laboratory of Virology (LIM-52-HCFMUSP), Institute of Tropical Medicine, University of São Paulo School of Medicine, São Paulo 05403-000, Brazil;
| | - Amanda Caroline Zarpellon
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo 05508-000, Brazil; (N.F.d.O.N.); (R.A.V.C.); (A.C.Z.); (M.W.C.)
| | - Matheus Willian Caetano
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo 05508-000, Brazil; (N.F.d.O.N.); (R.A.V.C.); (A.C.Z.); (M.W.C.)
| | - Debora Pallos
- School of Dentistry, University of Santo Amaro, São Paulo 04743-030, Brazil;
| | - Roger Junges
- Institute of Oral Biology, Faculty of Dentistry, University of Oslo, 0316 Oslo, Norway;
| | - André Luiz Ferreira Costa
- Postgraduate Program in Dentistry, Cruzeiro do Sul University (UNICSUL), São Paulo 1506-000, Brazil;
| | - Juan Aitken-Saavedra
- Department of Oral Pathology and Medicine, Faculty of Dentistry, University of Chile, Santiago 3311, Chile;
| | - Simone Giannecchini
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Paulo Henrique Braz-Silva
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo 05508-000, Brazil; (N.F.d.O.N.); (R.A.V.C.); (A.C.Z.); (M.W.C.)
- Laboratory of Virology (LIM-52-HCFMUSP), Institute of Tropical Medicine, University of São Paulo School of Medicine, São Paulo 05403-000, Brazil;
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Dülek Ö, Mutlu G, Koçkaya ES, Can H, Karakavuk M, Değirmenci Döşkaya A, Gürüz AY, Döşkaya M, Ün C. Computational identification of monkeypox virus epitopes to generate a novel vaccine antigen against Mpox. Biologicals 2024; 88:101798. [PMID: 39471737 DOI: 10.1016/j.biologicals.2024.101798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 09/12/2024] [Accepted: 10/16/2024] [Indexed: 11/01/2024] Open
Abstract
Monkeypox virus (MPXV) belonging to poxviridae family causes chronic viral disease in various mammals including human and monkeys. Conventional vaccines developed against smallpox of poxviridae, are not specific against Mpox. Also, they can cause various side effects after vaccination. In this study, we aimed to analyze the A17L, A28L, A37R, A43R, E8L, H3L, B6R, and M1R structural proteins of MPXV and identify epitopes in them which can be used to generate vaccine antigens. Among the proteins analyzed, the M1R protein was predicted to be more appropriate for use in vaccine research due to its high antigenicity value and other physicochemical features. Also, A17L, B6R and E8L had high antigenicity values. E8L protein was more conserved while the A37R, A43R, and B6R proteins had signal peptides. Although a total of eight B cell epitopes were predicted in all proteins analyzed, CNGETK epitope belonging to B6R protein had the highest antigenicity value (1.7083), as well as was non-allergenic, non-toxic, and soluble. Based on T cell epitope analyses performed on all proteins, fourteen MHC-I/II epitopes were predicted that are antigenic, non-allergenic and non-toxic, as well as soluble. Among them, MHC-I related-HEIYDRNVGF epitope in A28L protein had the highest antigenicity value (1.6650) and MHC-II related-IGNIKIVQIDIRDIK epitope in A37R protein had the highest antigenicity value (2.0280). In conclusion, eight structural proteins of MPXV were successfully analyzed and 22 important epitopes were identified that could serve as vaccine antigens or in serological studies to develop diagnostic tools.
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Affiliation(s)
- Özge Dülek
- Ege University Faculty of Science, Department of Biology, Molecular Biology Section, İzmir, Turkiye
| | - Gizem Mutlu
- Ege University Institute of Health Sciences, Department of Vaccine Studies, İzmir, Turkiye; Ege University Vaccine Development Application and Research Center, İzmir, Turkiye
| | - Ecem Su Koçkaya
- Ege University Faculty of Science, Department of Biology, Molecular Biology Section, İzmir, Turkiye
| | - Hüseyin Can
- Ege University Faculty of Science, Department of Biology, Molecular Biology Section, İzmir, Turkiye; Ege University Institute of Health Sciences, Department of Vaccine Studies, İzmir, Turkiye; Ege University Vaccine Development Application and Research Center, İzmir, Turkiye.
| | - Muhammet Karakavuk
- Ege University Institute of Health Sciences, Department of Vaccine Studies, İzmir, Turkiye; Ege University Vaccine Development Application and Research Center, İzmir, Turkiye; Ege University Ödemiş Vocational School, İzmir, Turkiye
| | - Aysu Değirmenci Döşkaya
- Ege University Institute of Health Sciences, Department of Vaccine Studies, İzmir, Turkiye; Ege University Vaccine Development Application and Research Center, İzmir, Turkiye; Ege University Faculty of Medicine, Department of Parasitology, İzmir, Turkiye
| | - Adnan Yüksel Gürüz
- Ege University Institute of Health Sciences, Department of Vaccine Studies, İzmir, Turkiye; Ege University Vaccine Development Application and Research Center, İzmir, Turkiye; Ege University Faculty of Medicine, Department of Parasitology, İzmir, Turkiye
| | - Mert Döşkaya
- Ege University Institute of Health Sciences, Department of Vaccine Studies, İzmir, Turkiye; Ege University Vaccine Development Application and Research Center, İzmir, Turkiye; Ege University Faculty of Medicine, Department of Parasitology, İzmir, Turkiye
| | - Cemal Ün
- Ege University Faculty of Science, Department of Biology, Molecular Biology Section, İzmir, Turkiye; Ege University Institute of Health Sciences, Department of Vaccine Studies, İzmir, Turkiye; Ege University Vaccine Development Application and Research Center, İzmir, Turkiye
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Pham TTD, Thai QM, Tuyen PNK, Phung HTT, Ngo ST. Computational discovery of tripeptide inhibitors targeting monkeypox virus A42R profilin-like protein. J Mol Graph Model 2024; 132:108837. [PMID: 39098150 DOI: 10.1016/j.jmgm.2024.108837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/06/2024]
Abstract
Monkeypox is an infectious disease caused by the monkeypox virus (MPXV), a member of the Orthopoxvirus genus closely related to smallpox. The structure of the A42R profilin-like protein is the first and only available structure among MPXV proteins. Biochemical studies of A42R were conducted in the 1990s and later work also analyzed the protein's function in viral replication in cells. This study aims to screen tripeptides for their potential inhibition of the A42R profilin-like protein using computational methods, with implications for MPXV therapy. A total of 8000 tripeptides underwent molecular docking simulations, resulting in the identification of 20 compounds exhibiting strong binding affinity to A42R. To validate the docking results, molecular dynamics simulations and free energy perturbation calculations were performed. These analyses revealed two tripeptides with sequences TRP-THR-TRP and TRP-TRP-TRP, which displayed robust binding affinity to A42R. Markedly, electrostatic interactions predominated over van der Waals interactions in the binding process between tripeptides and A42R. Three A42R residues, namely Glu9, Ser12, and Arg38, appear to be pivotal in mediating the interaction between A42R and the tripeptide ligands. Notably, tripeptides containing two or three tryptophan residues demonstrate a pronounced binding affinity, with the tripeptide comprising three tryptophan amino acids showing the highest level of affinity. These findings offer valuable insights for the selection of compounds sharing a similar structure and possessing a high affinity for A42R, potentially capable of inhibiting its enzyme activity. The study highlights a structural advantage and paves the way for the development of targeted therapies against MPXV infections.
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Affiliation(s)
- Thi-Thuy-Duong Pham
- Faculty of Environment, Saigon University, 273 An Duong Vuong, Ward 3, District 5, Ho Chi Minh City, 70000, Viet Nam
| | - Quynh Mai Thai
- Laboratory of Biophysics, Institute for Advanced Study in Technology, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Viet Nam
| | - Pham Nguyen Kim Tuyen
- Faculty of Environment, Saigon University, 273 An Duong Vuong, Ward 3, District 5, Ho Chi Minh City, 70000, Viet Nam
| | - Huong Thi Thu Phung
- NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, Viet Nam.
| | - Son Tung Ngo
- Laboratory of Biophysics, Institute for Advanced Study in Technology, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Viet Nam.
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Hafeez U, Kant SB, Sakina S, Khan Raja S, Akbar A, Khattak MI, Ahmed M, Jadoon SK, Tasneem S. Knowledge, Attitude, and Behavior of the Pakistani Population Toward the Monkeypox Pandemic and the Associated Factors. Cureus 2024; 16:e73061. [PMID: 39640178 PMCID: PMC11619807 DOI: 10.7759/cureus.73061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/05/2024] [Indexed: 12/07/2024] Open
Abstract
Background Monkeypox (Mpox) is a virulent disease caused by orthopoxvirus. Mpox is emerging as a major global health threat. Currently, more than 100 countries are facing outbreaks. Pakistan, too, is witnessing the spread of this virus, with 11 confirmed cases and one death since its first detection in April 2023. Mpox infection can be diagnosed using polymerase chain reaction (PCR) and treated with antiviral agents. The smallpox vaccine is also proven to be effective against Mpox. Methodology This cross-sectional survey aimed to evaluate the knowledge, attitude, and behaviors (KAB) of the Pakistani population toward the Mpox pandemic and determine the factors affecting it. Data were collected through Google Forms using a validated questionnaire to assess the population's KAB. In total, 1,511 individuals were included in the final analysis. Results Study participants had good knowledge of the disease, poor attitude toward Mpox risk and severity, and poor behavior with low adherence to recommended protocols. Overall, 58% (n = 888) of the participants were male, and most of the respondents were aged between 18 and 30 years (n = 743, 49.2%). Most participants were married (n = 983, 65.1%), from urban areas (n = 837, 55.4%), and living in shared households (n = 876, 58%). Age showed a significant relationship with knowledge level and behavior, but not with attitude. The 18-30-year age group demonstrated higher knowledge levels (p = 0.007), regardless of gender. Shared households were significantly associated with a higher incidence of good knowledge (p < 0.05) compared to independent households (p = 0.038). Additionally, higher income was linked to better attitudes and behaviors. KAB outcomes also varied significantly based on marital status, individual education level, and parents' education levels. Conclusions Population dynamics such as cultural norms, religious beliefs, misperceptions about the disease associated with sexual behavior, health literacy, education level, rural and urban division of the population, gender role, migrant and refugee population, poverty, cost-seeking healthcare, and distrust in the government and healthcare system should be considered when constructing a public health policy because the behavior of the population is important for the implementation of preventive measures.
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Affiliation(s)
- Uzma Hafeez
- Public Health/Community Medicine, Azad Jammu Kashmir Medical College, Muzaffarabad, PAK
| | - Sara Bashir Kant
- Public Health/Community Medicine, Azad Jammu Kashmir Medical College, Muzaffarabad, PAK
| | | | - Sohail Khan Raja
- Pulmonology, Azad Jammu Kashmir Medical College, Muzaffarabad, PAK
| | - Amna Akbar
- Emergency and Accident, District Headquarter Hospital, Jhelum Valley, Muzaffarabad, PAK
| | | | - Mumtaz Ahmed
- Pathology, Azad Jammu Kashmir Medical College, Muzaffarabad, PAK
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Protopapas K, Dimopoulou D, Kalesis N, Akinosoglou K, Moschopoulos CD. Mpox and Lessons Learned in the Light of the Recent Outbreak: A Narrative Review. Viruses 2024; 16:1620. [PMID: 39459952 PMCID: PMC11512351 DOI: 10.3390/v16101620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/11/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
According to the WHO, more than 90,000 cases of mpox have been reported since the 2022 worldwide outbreak, which resulted in 167 deaths, while a new outbreak in Africa since 2023 has resulted in over 18,000 cases and 617 deaths. Mpox is a zoonosis caused by the monkeypox virus, a double-stranded DNA virus belonging to the Orthopoxvirus genus, which causes smallpox-like illness. Until 2022, cases were predominately located in West and Central Africa, with only sporadic cases and outbreaks reported in other parts of the world. During the 2022 outbreak, the primary mode of transmission was sexual contact among men who have sex with men. The changing epidemiology of mpox resulted in new disease phenotypes and populations at risk, disproportionally affecting people who live with HIV. Commonly presenting as a mild, self-limiting illness, mpox can cause severe and protracted disease in people with HIV with a CD4 count < 200 cell/mm3. The global emergence of mpox that followed and intersected with COVID-19 mobilized the scientific community and healthcare stakeholders to provide accurate diagnostics, preventive vaccines and treatment to those most affected. Despite existing gaps, this rapid response helped to contain the outbreak, but challenges remain as new variants emerge. Preparedness and readiness to respond to the next outbreak is crucial in order to minimize the impact to the most vulnerable.
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Affiliation(s)
- Konstantinos Protopapas
- Fourth Department of Internal Medicine, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (K.P.); (C.D.M.)
| | - Dimitra Dimopoulou
- Second Department of Pediatrics, “Aghia Sophia” Children’s Hospital, 11527 Athens, Greece;
| | - Nikolaos Kalesis
- Dermatology Department, General Hospital of Nikaia-Piraeus ‘Agios Panteleimon’, General Hospital of West Attica ‘Agia Varvara’, 12351 Athens, Greece;
| | | | - Charalampos D. Moschopoulos
- Fourth Department of Internal Medicine, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (K.P.); (C.D.M.)
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Ghazy RM, Hussein M, Abdu SMM, El-Sayed Ellakwa D, Tolba MM, Youssef N, Mahboob AS, Abd ElHafeez S. The intention of Egyptian healthcare workers to take the monkeypox vaccine: is urgent action required? BMC Health Serv Res 2024; 24:1204. [PMID: 39379920 PMCID: PMC11462741 DOI: 10.1186/s12913-024-11147-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 05/24/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND In light of the ongoing monkeypox (MPOX) epidemic, healthcare workers (HCWs) have been in contact with various diseases. Therefore, they should take appropriate preventive and control measures to maintain their health. This study assessed Egyptian HCWs' intentions to take MPOX vaccines. METHODS A cross-sectional survey was conducted using social media platforms between September 27 and November 4, 2022. An anonymous online survey using the 5C scale was conducted using convenience and snowball sampling methods to assess the five psychological antecedents of vaccination (i.e., confidence, constraints, complacency, calculation, and collective responsibility). RESULTS A total of 399 HCWs with a mean age of 32.6 ± 5.7 participated in this study. Of them, 89.7% were female. The five C psychological antecedents of vaccination were as follows: 55.9% were confident about vaccination, 50.6% were complacent, 56.6% experienced constraints, 60.7% calculated the risk and benefit, and 58.4% had collective responsibility. Multivariate analysis showed that high income level and having information about MPOX were significant predictors of confidence in the MPOX vaccines (adjusted odds ratio ((AOR) = 4.19, 95% CI (1.12- 15.59), P = 0.032). Participants aged 31-45 years and 19-30 years showed significant association (AOR = 2.46, 95% CI (0.85-7.15), P = 0.096) and (AOR = 4.19, 95% CI (1.39-12.64), P = 0.011), respectively. Having an idea about the MPOX vaccines significantly predicted the complacency domain (AOR = 3.77, 95%CI (1.47-9.65, P = 0.006). Moreover, precollege/undergraduate education and having an idea about MPOX vaccination were significant predictors of the constraint domain (AOR = 1.81.95% CI (1.09-2.99, P = 0.020), (AOR = 2.70, 95% CI (1.05-6.95, P = 0.038), respectively). Female sex, having a diploma, postgraduate studies, and having an idea about MPOX vaccine significantly predicted calculation domain (AOR = 2.06, 95% CI (1.05-4.04, P = 0.035), (AOR = 3.98,95% CI (1.33-11.87, P = 0.013), (AOR = 2.02, 95% CI (1.25-3.26, P = 0.004) & (AOR = 2.75. 95% CI (1.05-7.18, P = 0.039), respectively. The only significant predictor of collective responsibility was having a diploma and postgraduate studies (AOR = 3.44, 95% CI (1.21-9.78, P = 0.020), (AOR = 1.90,95% CI (1.17-3.09, P = 0.009). CONCLUSIONS Efforts to control MPOX should focus on promoting protective measures such as the vaccination of HCWs as well as raising their awareness about the updated information regarding the virus and the approved vaccines.
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Affiliation(s)
- Ramy Mohamed Ghazy
- Tropical Health, High Institute of Public Health, Alexandria University, Alexandria, Egypt
| | - Mai Hussein
- Alexandria Clinical Research Administration, Alexandria Health Affairs Directorate, Alexandria, Egypt.
- Ministry of Health and Population, Cairo, Egypt.
| | | | - Doha El-Sayed Ellakwa
- Biochemistry Department Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
- Department of Biochemistry, Faculty of Pharmacy, Sinai University, Kantara Branch, Ismailia, Egypt
| | - Mahmoud M Tolba
- Pharmaceutical Division, Ministry of Health and Population, Cairo, Egypt
| | - Naglaa Youssef
- Medical-Surgical Nursing Department, Faculty of Nursing, Cairo University, Cairo, Egypt
| | - Amira Saad Mahboob
- Department of Occupational Health and Industrial Medicine, High Institute of Public Health, Alexandria University, Alexandria, Egypt
| | - Samar Abd ElHafeez
- Epidemiology Department, High Institute of Public Health, Alexandria University, Alexandria, Egypt
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Wang Y, Beltran RM, Cumberland WG, Young SD. Factors Associated with COVID-19 Testing, Vaccination, and Use of Digital Contact Tracing Apps among Black and Latinx MSM (BLMSM) in Los Angeles. J Racial Ethn Health Disparities 2024; 11:2925-2934. [PMID: 37566181 PMCID: PMC10953315 DOI: 10.1007/s40615-023-01750-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 08/12/2023]
Abstract
This study examines the factors associated with COVID-19 testing, vaccination intent (both individually and jointly), and willingness to use contact tracing digital apps among a cohort of Black and Latinx men who have sex with men (BLMSM) living in Los Angeles during the initial peak (July 2020) of the COVID-19 pandemic. A questionnaire detailing participants COVID-19 experiences was sent to 300 primarily BLMSM after the first state-wide COVID-19 lockdown. Logistic regression models with random cluster effects were used for analyses. Forty-two percent (42%) tested for COVID-19, 27% were willing to get vaccinated, and about 45% reported willingness to use contact tracing digital apps. Controlling for intervention participation, age, education, marital status, employment, health, tobacco, binge drinking, and self-reported anxiety, those who were depressed had 33% (95% CI: 0.13 to 0.82) odds of using a prevention strategy (either test for COVID-19 or vaccination intent) as the group who were not depressed. Those who had high school diploma or less had 23% (95% CI: 0.11 to 0.48) odds to use digital contact tracing apps as the group with education level of at least Associate's or Bachelor's degree. Without considering the format of the test kits, vaccine side effects, and ease of use for digital contact tracing apps, participants appeared to still be hesitant in using COVID-19 prevention strategies at the initial height of the pandemic. Our findings suggest the need for further investigation into this hesitancy to better inform and prepare for future epidemics.
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Affiliation(s)
- Yan Wang
- Section of Public and Population Health, Division of Oral and Systemic Health Sciences, School of Dentistry, University of California, Los Angeles (UCLA), 10833 La Conte, Los Angeles, CA, 90095, USA.
| | - Raiza M Beltran
- Luskin School of Public Affairs, UCLA, 10833 La Conte, Los Angeles, CA, 90095, USA
| | - William G Cumberland
- Department of Biostatistics, Fielding School of Public Health, UCLA, 10833 La Conte, Los Angeles, CA, 90095, USA
| | - Sean D Young
- Department of Emergency Medicine, School of Medicine and Informatics, Information and Computer Sciences, University of California, Irvine, City Tower, Ste 640, Rt 128-01, Irvine, CA, 92697, USA
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Chakravarty N, Hemani D, Paravastu R, Ahmad Z, Palani SN, Arumugaswami V, Kumar A. Mpox Virus and its ocular surface manifestations. Ocul Surf 2024; 34:108-121. [PMID: 38972544 PMCID: PMC11625629 DOI: 10.1016/j.jtos.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/28/2024] [Accepted: 07/04/2024] [Indexed: 07/09/2024]
Abstract
The Mpox virus (MPXV) is the causative agent of human Mpox disease - a debilitating rash illness similar to smallpox. Although Clade I MPXV has remained endemic to West and Central Africa, Clade II MPXV has been responsible for many outbreaks worldwide. The most recent outbreak in 2022 resulted from the rapid spread of a new clade of MPXV, classified into Clade IIb - a distinct lineage from the previously circulating viral strains. The rapid spread and increased severity of Mpox disease by the Clade IIb strain have raised the serious public health imperative of better understanding the host and viral determinants during MPXV infection. In addition to typical skin rashes, including in the periorbital area, MPXV causes moderate to severe ophthalmic manifestations - most commonly, ocular surface complications (e.g., keratitis, conjunctivitis, blepharitis). While ocular manifestations of Clade I Mpox within the Congo basin have been well-reported, global incidence trends of ocular Mpox cases by Clade IIb are still emerging. Given the demonstrated ability of all MPXV strains to auto-inoculate ocular tissue, alongside the enhanced transmissibility of the Clade IIb virus, there is an urgent need to elucidate the mechanisms by which MPXV causes ocular anomalies. In this review, we discuss the viral and genomic structures of MPXV, the epidemiology, and pathology of systemic and ocular Mpox, as well as potential prophylactic and therapeutic interventions.
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Affiliation(s)
- Nikhil Chakravarty
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; School of Medicine, California University of Science and Medicine, Colton, CA, USA
| | - Darshi Hemani
- Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI, USA
| | - Ramya Paravastu
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Zeeshan Ahmad
- Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI, USA
| | - Sankara Naynar Palani
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Vaithilingaraja Arumugaswami
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
| | - Ashok Kumar
- Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI, USA.
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Liang H, Chen C, Liu T, Dong W, Li L. Quantitative detection of mpox antigen using time-resolved fluorescence immunochromatography. Biotechnol Appl Biochem 2024; 71:1025-1031. [PMID: 38689530 DOI: 10.1002/bab.2594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 04/19/2024] [Indexed: 05/02/2024]
Abstract
Recently, concern has been raised about the spread of human mpox virus, and the demand for rapid detection reagents for mpox virus has increased. This study aims to establish a time-resolved fluorescence immunochromatography (TRFICO) method for qualitative/quantitative detection of mpox virus. A double-antibody sandwich TRFICO method was optimized and established using mpox recombinant fusion antigen and its paired monoclonal antibody. The test performance of the method was evaluated using mpox fusion antigen and control serum, including sensitivity, linearity range, specificity, precision, and reference interval. We successfully established a TRFICO method for qualitative/quantitative detection of mpox antigen, its linearity range 0-100 ng/mL, analytical sensitivity 0.017 ng/mL, and reference intervals greater than 0.045 ng/mL. No cross-reaction was detected with various poxvirus and clinical negative controls, with good specificity. All average recoveries of the intra- and inter-batch ranged from 81.33% to 97.83%, and all CVs were below 10%. Additionally, the TRFICO strips can be stably stored at 37°C for 7 days without significant changes in the fluorescence intensity. This TRFICO method, with high sensitivity, linearity range, specificity, precision, and stability with 16-min detection time, provides a new option for qualitative/quantitative and convenient testing of mpox virus.
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Affiliation(s)
- Huankun Liang
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, China
| | - Cuicui Chen
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, China
- Jinan Laide Bio-technology Co., Ltd, Jinan, China
| | - Tiancai Liu
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Wenqi Dong
- Guangzhou Zhenda Biopharmaceutical Technology Co., Ltd, Guangzhou, China
| | - Laiqing Li
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, China
- Jinan Laide Bio-technology Co., Ltd, Jinan, China
- Guangzhou Zhenda Biopharmaceutical Technology Co., Ltd, Guangzhou, China
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Avila MY, Gallego-Suarez LJ. Confocal Microscopy, Anterior Segment Optical Coherence Tomography and Clinical Findings in a Non-Granulomatous Uveitis Case for Mpox Infection. Ocul Immunol Inflamm 2024; 32:1901-1903. [PMID: 37831890 DOI: 10.1080/09273948.2023.2264388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 07/26/2023] [Accepted: 09/24/2023] [Indexed: 10/15/2023]
Abstract
PURPOSE To report a rare case of non-granulomatous anterior uveitis (clinical, IVCM in vivo confocal microscopy, and anterior optical coherence tomography (OCT) findings) in a non-immunosuppressed patient with mpox infection. METHODS A 24-year-old male was consulted for bilateral ocular pain, red eye, itchiness, and mucoid discharge. In his left eye, multiple vesicles and papules, some with central ulceration, were found in the superior and inferior eyelids. Mucoid discharge, chemosis, limbitis, and an anterior chamber reaction were also found. A conjunctival PCR swab for mpox was positive. The patient was treated with topical steroids with a good response. RESULTS OCT and IVCM showed sub-endothelial deposits, stromal edema, hyperreflective multinucleated images in the epithelial layer, activated stromal images, and stromal edema characterized by fusiform hyperreflectivity that was resolved with the proposed treatment. CONCLUSIONS This is the first report of OCT and IVCM in a non-immunosuppressed patient with mpox infection with a good response to topical steroids.
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Affiliation(s)
- Marcel Y Avila
- Department of Ophthalmology, School of Medicine Universidad Nacional de Colombia, Bogotá, Colombia
| | - Laura J Gallego-Suarez
- Department of Ophthalmology, School of Medicine Universidad Nacional de Colombia, Bogotá, Colombia
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Yi XM, Lei YL, Li M, Zhong L, Li S. The monkeypox virus-host interplays. CELL INSIGHT 2024; 3:100185. [PMID: 39144256 PMCID: PMC11321328 DOI: 10.1016/j.cellin.2024.100185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 07/11/2024] [Accepted: 07/11/2024] [Indexed: 08/16/2024]
Abstract
Monkeypox virus (MPXV) is a DNA virus belonging to the Orthopoxvirus genus within the Poxviridae family which can cause a zoonotic infection. The unexpected non-endemic outbreak of mpox in 2022 is considered as a new global threat. It is imperative to take proactive measures, including enhancing our understanding of MPXV's biology and pathogenesis, and developing novel antiviral strategies. The host immune responses play critical roles in defensing against MPXV infection while the virus has also evolved multiple strategies for immune escape. This review summarizes the biological features, antiviral immunity, immune evasion mechanisms, pathogenicity, and prevention strategies for MPXV.
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Affiliation(s)
- Xue-Mei Yi
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences, Wuhan University, Wuhan, 430071, China
| | - Ya-Li Lei
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences, Wuhan University, Wuhan, 430071, China
| | - Mi Li
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences, Wuhan University, Wuhan, 430071, China
| | - Li Zhong
- Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA
| | - Shu Li
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences, Wuhan University, Wuhan, 430071, China
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41
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Grajales DB, Kar S. Exploring Monkeypox: prospects for therapeutics through computational-aided drug discovery. Mol Divers 2024; 28:3497-3521. [PMID: 38079063 DOI: 10.1007/s11030-023-10767-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/06/2023] [Indexed: 12/05/2024]
Abstract
Monkeypox virus (MPXV) has emerged as a significant public health concern due to its potential for human transmission and its severe clinical manifestations. This review synthesizes findings from peer-reviewed articles spanning the last two decades, shedding light on diverse aspects of MPXV research. The exploration commences with an analysis of transmission dynamics, including zoonotic and human-to-human transmission, and potential reservoir hosts. Detailed insights into viral replication mechanisms illuminate its influence on disease progression and pathogenicity. Understanding the genomic and virion structure of MPXV is pivotal for targeted interventions. Genomic characteristics contributing to virulence are examined, alongside recent advancements in virion structure elucidation through cutting-edge imaging techniques. Emphasizing combat strategies, the review lists potential protein targets within the MPXV lifecycle for computer-aided drug design (CADD). The role of protein-ligand interactions and molecular docking simulations in identifying potential drug candidates is highlighted. Despite the absence of approved MPXV medications, the review outlines updates on ongoing small molecules and vaccine development efforts, spanning traditional and innovative platforms. The evolving landscape of computational drug research for MPXV is explored, encompassing advanced algorithms, machine learning, and high-performance computing. In conclusion, this review offers a holistic perspective on MPXV research by integrating insights spanning transmission dynamics to drug design. Equipping researchers with multifaceted understanding underscore the importance of innovative methodologies and interdisciplinary collaborations in addressing MPXV's challenges as research advances.
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Affiliation(s)
- Daniela Bermeo Grajales
- Chemometrics and Molecular Modeling Laboratory, Department of Chemistry, Kean University, 1000 Morris Avenue, Union, NJ, 07083, USA
| | - Supratik Kar
- Chemometrics and Molecular Modeling Laboratory, Department of Chemistry, Kean University, 1000 Morris Avenue, Union, NJ, 07083, USA.
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Rahmani E, Bayat Z, Farrokhi M, Karimian S, Zahedpasha R, Sabzehie H, Ramezani Poor S, Jafari Khouzani P, Aminpour S, Karami M, Afsharjahanshahi O, Sharifi M, Dalvandi B, Dalvandi R, Esfahani A, Alaei M, Mirbolouk M, Moradi F, Nozari A, Mirabedini SMS, Janmohamadi M, Moghimi S, Nikfarjam F, Jalayer Sarnaghy F, Mirbolook A, Pirouzan M, Mohammadi Virsoudi M, Moghadam Fard A, Nikandishnobar M, Boustani Hezarani H, Fadavighafari M, Farrokhi M. Monkeypox: A Comprehensive Review of Virology, Epidemiology, Transmission, Diagnosis, Prevention, Treatment, and Artificial Intelligence Applications. ARCHIVES OF ACADEMIC EMERGENCY MEDICINE 2024; 12:e70. [PMID: 39296520 PMCID: PMC11408898 DOI: 10.22037/aaem.v12i1.2491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 09/21/2024]
Abstract
Monkeypox (Mpox), an uncommon zoonotic Orthopoxvirus, is commonly manifested by blisters on the skin and has a mortality rate of approximately 0-10%. Approximately two decades after the cessation of global smallpox vaccination, the number of confirmed cases of Mpox has been growing, making it the most common Orthopoxvirus infection. Therefore, in this narrative review, we aimed to shed light on recent advancements in the pathophysiology, transmission routes, epidemiology, manifestations, diagnosis, prevention, and treatment of Mpox, as well as the application of artificial intelligence (AI) methods for predicting this disease. The clinical manifestations of Mpox, including the onset of symptoms and dermatologic characteristics, are similar to those of the infamous smallpox, but Mpox is clinically milder. Notably, a key difference between smallpox and Mpox is the high prevalence of lymphadenopathy. Human-to-human, animal-to-human, and animal-to-animal transmission are the three main pathways of Mpox spread that must be considered for effective prevention, particularly during outbreaks. PCR testing, as the preferred method for diagnosing Mpox infection, can enhance early detection of new cases and thereby improve infection control measures. JYNNEOS and ACAM2000 are among the vaccines most commonly recommended for the prevention of Mpox. Brincidofovir, Cidofovir, and Tecovirimat are the primary treatments for Mpox cases. Similar to other viral infections, the best approach to managing Mpox is prevention. This can, in part, be achieved through measures such as reducing contact with individuals displaying symptoms, maintaining personal safety, and adhering to practices commonly used to prevent sexually transmitted infections.
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Affiliation(s)
- Erfan Rahmani
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mehrdad Farrokhi
- Student Research Committee, Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Reza Zahedpasha
- Department of Radiology, School of Medicine, 5th Azar Hospital, Gorgan, Golestan, Iran
| | - Hamed Sabzehie
- Kocaeli Health and Technology University, Kocaeli, Turkey
| | | | | | - Solmaz Aminpour
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
| | - Mohammad Karami
- Student, Nanjing Medical University, International School (SIE), Nanjing, China
| | | | - Maryam Sharifi
- City Dental College and Hospital, Dhaka University, Dhaka, Bangladesh
| | | | | | | | | | - Mahtab Mirbolouk
- School of Pharmacy, Cyprus International University, Nicosia, North Cyprus
| | | | | | | | | | - Sara Moghimi
- Department of Physiology, Tulane School of Medicine, Tulane University, New Orleans 70112, Louisiana, U.S.A
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Chebaibi M, Bourhia M, Amrati FEZ, Slighoua M, Mssillou I, Aboul-Soud MAM, Khalid A, Hassani R, Bousta D, Achour S, Benhida R, Daoud R. Salsoline derivatives, genistein, semisynthetic derivative of kojic acid, and naringenin as inhibitors of A42R profilin-like protein of monkeypox virus: in silico studies. Front Chem 2024; 12:1445606. [PMID: 39318419 PMCID: PMC11420140 DOI: 10.3389/fchem.2024.1445606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 08/26/2024] [Indexed: 09/26/2024] Open
Abstract
Monkeypox virus (MPV) infection has developed into a re-emerging disease, and despite the potential of tecovirimat and cidofovir drugs, there is currently no conclusive treatment. The treatment's effectiveness and cost challenges motivate us to use In Silico approaches to seek natural compounds as candidate antiviral inhibitors. Using Maestro 11.5 in Schrodinger suite 2018, available natural molecules with validated chemical structures collected from Eximed Laboratory were subjected to molecular docking and ADMET analysis against the highly conserved A42R Profilin-like Protein of Monkeypox Virus Zaire-96-I-16 (PDB: 4QWO) with resolution of 1.52 Å solved 3D structure. Compared to the FDA-approved Tecovirimat, molecular docking revealed that Salsoline derivatives, Genistein, Semisynthetic derivative of kojic acid, and Naringenin had strengthened affinity (-8.9 to -10 kcal/mol) to 4QWO, and the molecular dynamic's simulation confirmed their high binding stability. In support of these results, the hydrogen bond analysis indicated that the Salsoline derivative had the most robust interaction with the binding pockets of 4QWO among the four molecules. Moreover, the comparative free energy analyses using MM-PBSA revealed an average binding free energy of the complexes of Salsoline derivative, Genistein, Semisynthetic derivative of kojic acid, Naringenin, of -106.418, -46.808, -50.770, and -63.319 kJ/mol, respectively which are lower than -33.855 kJ/mol of the Tecovirimat complex. Interestingly, these results and the ADMET predictions suggest that the four compounds are promising inhibitors of 4QWO, which agrees with previous results showing their antiviral activities against other viruses.
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Affiliation(s)
- Mohamed Chebaibi
- Ministry of Health and Social Protection, Higher Institute of Nursing Professions and Health Techniques, Fez, Morocco
| | - Mohammed Bourhia
- Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, Morocco
| | - Fatima ez-zahra Amrati
- Laboratory of Biotechnology, Environment, Agri-Food, and Health (LBEAS), Faculty of Sciences, University Sidi-Mohamed-Ben-Abdellah (USMBA), Fez, Morocco
| | - Meryem Slighoua
- Laboratory of Biotechnology, Environment, Agri-Food, and Health (LBEAS), Faculty of Sciences, University Sidi-Mohamed-Ben-Abdellah (USMBA), Fez, Morocco
| | - Ibrahim Mssillou
- Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life (SNAMOPEQ), Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco
| | - Mourad A. M. Aboul-Soud
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Asaad Khalid
- Health Research Center, Jazan University, Jazan, Saudi Arabia
| | - Rym Hassani
- Environment and Nature Research Centre, Jazan University, Jazan, Saudi Arabia
| | - Dalila Bousta
- National Agency of Medicinal and Aromatic Plants Tounate, Taounate, Morocco
| | - Sanae Achour
- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy of Fez, Sidi Mohamed Ben Abdellah University, Fez, Morocco
| | - Rachid Benhida
- Chemical and Biochemical Sciences-Green Processing Engineering, Mohammed VI Polytechnic University, Ben Guerir, Morocco
| | - Rachid Daoud
- Chemical and Biochemical Sciences-Green Processing Engineering, Mohammed VI Polytechnic University, Ben Guerir, Morocco
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Pashazadeh Azari P, Rezaei Zadeh Rukerd M, Charostad J, Bashash D, Farsiu N, Behzadi S, Mahdieh Khoshnazar S, Heydari S, Nakhaie M. Monkeypox (Mpox) vs. Innate immune responses: Insights into evasion mechanisms and potential therapeutic strategies. Cytokine 2024; 183:156751. [PMID: 39244831 DOI: 10.1016/j.cyto.2024.156751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 08/16/2024] [Accepted: 09/04/2024] [Indexed: 09/10/2024]
Abstract
Orthopoxviruses, a group of zoonotic viral infections, have emerged as a significant health emergency and global concern, particularly exemplified by the re-emergence of monkeypox (Mpox). Effectively addressing these viral infections necessitates a comprehensive understanding of the intricate interplay between the viruses and the host's immune response. In this review, we aim to elucidate the multifaceted aspects of innate immunity in the context of orthopoxviruses, with a specific focus on monkeypox virus (MPXV). We provide an in-depth analysis of the roles of key innate immune cells, including natural killer (NK) cells, dendritic cells (DCs), and granulocytes, in the host defense against MPXV. Furthermore, we explore the interferon (IFN) response, highlighting the involvement of toll-like receptors (TLRs) and cytosolic DNA/RNA sensors in detecting and responding to the viral presence. This review also examines the complement system's contribution to the immune response and provides a detailed analysis of the immune evasion strategies employed by MPXV to evade host defenses. Additionally, we discuss current prevention and treatment strategies for Mpox, including pre-exposure (PrEP) and post-exposure (PoEP) prophylaxis, supportive treatments, antivirals, and vaccinia immune globulin (VIG).
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Affiliation(s)
- Pouya Pashazadeh Azari
- Department of Immunology, Faculty of Medicine, Kerman University of Medical Science, Kerman, Iran
| | - Mohammad Rezaei Zadeh Rukerd
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Javad Charostad
- Department of Microbiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Niloofar Farsiu
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Saleh Behzadi
- Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Seyedeh Mahdieh Khoshnazar
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Sajjad Heydari
- Department of Immunology, Faculty of Medicine, Kerman University of Medical Science, Kerman, Iran
| | - Mohsen Nakhaie
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran; Clinical Research Development Unit, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran.
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Majidifar S, Zabihian A, Hooshmand M. Combination therapy synergism prediction for virus treatment using machine learning models. PLoS One 2024; 19:e0309733. [PMID: 39231124 PMCID: PMC11373828 DOI: 10.1371/journal.pone.0309733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 08/16/2024] [Indexed: 09/06/2024] Open
Abstract
Combining different drugs synergistically is an essential aspect of developing effective treatments. Although there is a plethora of research on computational prediction for new combination therapies, there is limited to no research on combination therapies in the treatment of viral diseases. This paper proposes AI-based models for predicting novel antiviral combinations to treat virus diseases synergistically. To do this, we assembled a comprehensive dataset comprising information on viral strains, drug compounds, and their known interactions. As far as we know, this is the first dataset and learning model on combination therapy for viruses. Our proposal includes using a random forest model, an SVM model, and a deep model to train viral combination therapy. The machine learning models showed the highest performance, and the predicted values were validated by a t-test, indicating the effectiveness of the proposed methods. One of the predicted combinations of acyclovir and ribavirin has been experimentally confirmed to have a synergistic antiviral effect against herpes simplex type-1 virus, as described in the literature.
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Affiliation(s)
- Shayan Majidifar
- Department of Computer Science and Information Technology, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran
| | - Arash Zabihian
- Department of QA, Kimia Zist Parsian Pharmaceutical Company, Zanjan, Iran
| | - Mohsen Hooshmand
- Department of Computer Science and Information Technology, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran
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46
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Derhab N. Human monkeypox virus: A systematic critical review during the pandemic peak. Indian J Med Microbiol 2024; 51:100704. [PMID: 39134221 DOI: 10.1016/j.ijmmb.2024.100704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 08/05/2024] [Accepted: 08/10/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND In July 2022, the world health organization (WHO) announced the monkeypox virus (MPXV) as a public health emergency of international concern, due to the unprecedented global transmission of the disease beyond previously endemic countries in Africa. METHODS For this systematic review, the author searched the "web of science" (WoS) database, which retrieves 138 articles on MPXV, published between 01-04-2022 and 22-09-2022. This period witnessed the maximum cases of infection as confirmed by the WHO. Seventy articles were used for in-depth analysis, after excluding papers not highly relevant to the topic. RESULTS AND CONCLUSIONS The current review demonstrates different types of MPXV identification analysis, transmission of MPXV, clinical features, immune responses against MPXV, the mutations, and phylogenetic analysis. It also identifies the patients with high-risk complications and determines the other diseases related to MPXV. This paper provides suggestions for the suitable usage of vaccines or antiviral drugs as a procedure to control the outbreak and preventive strategies related to the humans. This research discusses significant implications and recommendations to contribute in reducing the spread of MPXV and presents avenues for upcoming MPXV research.
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Affiliation(s)
- Neama Derhab
- Department of Botany and Microbiology, Faculty of Science, Damanhour University, Damanhour, Egypt.
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Mohapatra RK, Mahal A, Mohapatra PK, Sarangi AK, Mishra S, Alsuwat MA, Alshehri NN, Abdelkhalig SM, Garout M, Aljeldah M, Alshehri AA, Saif A, Alshahrani MA, Alqahtani AS, Almutawif YA, Eid HM, Albaqami FM, Abdalla M, Rabaan AA. Structure-based discovery of F. religiosa phytochemicals as potential inhibitors against Monkeypox (mpox) viral protein. JOURNAL OF BIOSAFETY AND BIOSECURITY 2024; 6:157-169. [DOI: 10.1016/j.jobb.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/12/2025] Open
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48
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Kataria R, Duhan N, Kaundal R. Navigating the human-monkeypox virus interactome: HuPoxNET atlas reveals functional insights. Front Microbiol 2024; 15:1399555. [PMID: 39155985 PMCID: PMC11327128 DOI: 10.3389/fmicb.2024.1399555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 07/09/2024] [Indexed: 08/20/2024] Open
Abstract
Monkeypox virus, a close relative of variola virus, has significantly increased the incidence of monkeypox disease in humans, with several clinical symptoms. The sporadic spread of the disease outbreaks has resulted in the need for a comprehensive understanding of the molecular mechanisms underlying disease infection and potential therapeutic targets. Protein-protein interactions play a crucial role in various cellular processes and regulate different immune signals during virus infection. Computational algorithms have gained high significance in the prediction of potential protein interaction pairs. Here, we developed a comprehensive database called HuPoxNET (https://kaabil.net/hupoxnet/) using the state-of-the-art MERN stack technology. The database leverages two sequence-based computational models to predict strain-specific protein-protein interactions between human and monkeypox virus proteins. Furthermore, various protein annotations of the human and viral proteins such as gene ontology, KEGG pathways, subcellular localization, protein domains, and novel drug targets identified from our study are also available on the database. HuPoxNET is a user-friendly platform for the scientific community to gain more insights into the monkeypox disease infection and aid in the development of therapeutic drugs against the disease.
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Affiliation(s)
- Raghav Kataria
- Department of Plants, Soils, and Climate, College of Agriculture and Applied Sciences, Logan, UT, United States
- Bioinformatics Facility, Center for Integrated BioSystems, Logan, UT, United States
| | - Naveen Duhan
- Department of Plants, Soils, and Climate, College of Agriculture and Applied Sciences, Logan, UT, United States
- Bioinformatics Facility, Center for Integrated BioSystems, Logan, UT, United States
| | - Rakesh Kaundal
- Department of Plants, Soils, and Climate, College of Agriculture and Applied Sciences, Logan, UT, United States
- Bioinformatics Facility, Center for Integrated BioSystems, Logan, UT, United States
- Department of Computer Science, College of Science, Utah State University, Logan, UT, United States
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Mani S, Ganesan A, Arunagiri T, Ravi Kumaran V, Kannaiah KP, Vellapandian C, Chanduluru HK. Epidemiology, Virology, and Mutation Landscape of Monkeypox Virus From Past to Present. Cureus 2024; 16:e67872. [PMID: 39328711 PMCID: PMC11424752 DOI: 10.7759/cureus.67872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 08/26/2024] [Indexed: 09/28/2024] Open
Abstract
Monkeypox (Mpox) has emerged as a significant threat to the global population. Initially identified in a rural area of Africa in 1970, after the eradication of smallpox, it spread rapidly across various African nations. The ongoing evolution of the monkeypox virus (MPXV), which causes Mpox, and its potential for cross-species transmission led to a global outbreak in 2022. Despite the control measures during the outbreak, Mpox cases continue in several African nations, posing a persistent public health threat. Global surveillance is crucial to eradicating MPXV from human populations and preventing its resurgence. Factors contributing to MPXV's increased transmissibility and immune evasion include its mutation rate, adaptability, and genetic evolution. Therefore, understanding the epidemiology and virology of Mpox is essential for developing effective prevention and control strategies. This study explores the history of human Mpox, the complexity of MPXV, how it replicates, and drug-resistant mutations. It will also stress how important it is to study how the circadian clock affects virus replication in infectious diseases in order to effectively fight this new public health threat. Understanding these aspects is crucial for developing effective strategies against Mpox as well as addressing the challenges posed by genetic mutations and resistance. The compiled information in this review underscores the critical need for continued research and monitoring to tackle the evolving dynamics of Mpox and its broader impact on global health.
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Affiliation(s)
- Suganandhini Mani
- Pharmacy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, IND
| | - Alagammai Ganesan
- Pharmacy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, IND
| | - Thirumalai Arunagiri
- Pharmacy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, IND
| | - Vamsi Ravi Kumaran
- Pharmacy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, IND
| | | | - Chitra Vellapandian
- Pharmacy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, IND
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50
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Alharbi AS, Altwaim SA, El-Daly MM, Hassan AM, Al-Zahrani IA, Bajrai LH, Alsaady IM, Dwivedi VD, Azhar EI. Marine fungal diversity unlocks potent antivirals against monkeypox through methyltransferase inhibition revealed by molecular dynamics and free energy landscape. BMC Chem 2024; 18:141. [PMID: 39080756 PMCID: PMC11290312 DOI: 10.1186/s13065-024-01251-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 07/19/2024] [Indexed: 08/02/2024] Open
Abstract
The escalating threat posed by the Monkeypox virus (MPXV) to global health necessitates the urgent discovery of effective antiviral agents, as there are currently no specific drugs available for its treatment, and existing inhibitors are hindered by toxicity and poor pharmacokinetic profiles. This study aimed to identify potent MPXV inhibitors by screening a diverse library of small molecule compounds derived from marine fungi, focusing on the viral protein VP39, a key methyltransferase involved in viral replication. An extensive virtual screening process identified four promising compounds-CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569-alongside a control molecule. Rigorous evaluations, including re-docking, molecular dynamics (MD) simulations, and hydrogen bond analysis, were conducted to assess their inhibitory potential against MPXV VP39. CMNPD15724 and CMNPD30883, in particular, demonstrated a superior binding affinity and stable interactions within the target protein's active site throughout the MD simulations, suggesting a capacity to overcome the limitations associated with sinefungin. The stability of these VP39-compound complexes, corroborated by MD simulations, provided crucial insights into the dynamic behavior of these interactions. Furthermore, Principal Component Analysis (PCA) based free energy landscape assessments offered a detailed understanding of the dynamic conformational changes and energetic profiles underlying these compounds' functional disruption of VP39. These findings establish CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569 as promising MPXV inhibitors and highlight marine fungi as a valuable source of novel antiviral agents. These compounds represent potential candidates for further experimental validation, advancing the development of safer and more effective therapeutic options to combat this emerging viral infection.
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Affiliation(s)
- Azzah S Alharbi
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia.
- Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, 21362, Jeddah, Saudi Arabia.
| | - Sarah A Altwaim
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
- Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
| | - Mai M El-Daly
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
| | - Ahmed M Hassan
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
| | - Ibrahim A Al-Zahrani
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
| | - Leena H Bajrai
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
| | - Isra M Alsaady
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
| | - Vivek Dhar Dwivedi
- Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospitals, Saveetha University, Chennai, 605102, India.
- Bioinformatics Research Division, Quanta Calculus, Greater Noida, 201310, India.
| | - Esam I Azhar
- Special Infectious Agents Unit - BSL3, King Fahd Medical Research Center, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, 21362, Jeddah, Saudi Arabia
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