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Bakre A, Sweeney R, Espinoza E, Suarez DL, Kapczynski DR. The ACE2 Receptor from Common Vampire Bat ( Desmodus rotundus) and Pallid Bat ( Antrozous pallidus) Support Attachment and Limited Infection of SARS-CoV-2 Viruses in Cell Culture. Viruses 2025; 17:507. [PMID: 40284950 PMCID: PMC12031370 DOI: 10.3390/v17040507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/26/2025] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
During the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SC2) infection was confirmed in various animal species demonstrating a wide host range of the virus. Prior studies have shown that the ACE2 protein is the primary receptor used by the virus to gain cellular entry and begin the replication cycle. In previous studies, we demonstrated that human and various bat ACE2 proteins can be utilized by SC2 viruses for entry. Bats are a suspected natural host of SC2 because of genetic homology with other bat coronaviruses. In this work, we demonstrate that expression of ACE2 genes from the common vampire bat (CVB) (Desmodus rotundus) and the pallid bat (PB) (Antrozous pallidus), supports infection and replication of some SC2 viruses in cell culture. Two cell lines were produced, CVB-ACE2 and PB-ACE2, expressing ACE2 from these bat species along with human TMPRSS2, in a model previously established using a non-permissive chicken DF-1 cell line. Results demonstrate that the original Wuhan lineage (WA1) virus and the Delta variant were able to infect and replicate in either of the bat ACE2 cell lines. In contrast, the Lambda and Omicron variant viruses infected both cell lines, but viral titers did not increase following infection. Viral detection using immunofluorescence demonstrated abundant spike (S) protein staining for the WA1 and Delta variants but little signal for the Lambda and Omicron variants. These studies demonstrate that while ACE2 from CVB and PB can be utilized by SC2 viruses to gain entry for infection, later variants (Lambda and Omicron) replicate poorly in these cell lines. These observations suggest more efficient human adaption in later SC2 variants that become less fit for replication in other animal species.
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Affiliation(s)
- Abhijeet Bakre
- Exotic and Emerging Avian Viral Disease Research Unit, Southeast Poultry Research Laboratories, US National Poultry Research Center, United States Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA; (R.S.); (E.E.); (D.L.S.); (D.R.K.)
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Sarangi AK, Salem MA, Younus MD, El-Haroun H, Mahal A, Tripathy L, Mishra R, Shabil M, Alhumaydhi FA, Khatib MN, Bushi G, Rustagi S, Dey D, Satapathy P, Ballal S, Bansal P, Bhopte K, Tomar BS, Mishra S, Alissa M, Mohapatra RK, El-Bahy ZM. Advanced biomaterials for regenerative medicine and their possible therapeutic significance in treating COVID-19: a critical overview. Int J Surg 2024; 110:7508-7527. [PMID: 39411890 PMCID: PMC11634172 DOI: 10.1097/js9.0000000000002110] [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: 05/10/2024] [Accepted: 09/27/2024] [Indexed: 12/13/2024]
Abstract
The potential of biomaterials in medical sciences has attracted much interest, especially in promoting tissue regeneration and controlling immune responses. As the COVID-19 pandemic broke out, there was an increased interest in understanding more about how biomaterials could be employed to fight this dreaded disease, especially in the context of regenerative medicine. Out of the numerous regenerative medicine possibilities, stem cells and scaffolding (grafting) technology are two major areas in modern medicine and surgery. Mesenchymal stem cells are useful in tissue repair, tailored therapy and the treatment of COVID-19. Using biomaterials in COVID-19 treatment is intricate and needs multidisciplinary and cross-disciplinary research. Cell-based therapy and organ transplants pose immunological rejection challenges. Immunomodulation enhanced, tumorigenicity decreased, inflammation addressed and tissue damage restricted; bioengineered stem cells need clinical insights and validation. Advanced stem cell-based therapies should ideally be effective, safe and scalable. Cost and scalability shall dictate the dawn of techno-economically feasible regenerative medicine. A globally standard and uniform approval process could accelerate translational regenerative medicine. Researchers, patient advocacy organisations, regulators and biopharmaceutical stakeholders need to join hands for easy navigation of regulatory measures and expeditious market entry of regenerative medicine. This article summarises advances in biomaterials for regenerative medicine and their possible therapeutic benefits in managing infectious diseases like COVID-19. It highlights the significant recent developments in biomaterial design, scaffold construction, and stem cell-based therapies to treat tissue damage and COVID-19-linked immunological dysregulation. It also highlights the potential contribution of biomaterials towards creating novel treatment strategies to manage COVID-19.
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Affiliation(s)
- Ashish K. Sarangi
- Department of Chemistry, Centurion University of Technology and Management, Balangir, Odisha, India
| | - Mohamed A. Salem
- Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail, Assir, Saudi Arabia
| | - Mustafa D. Younus
- Department of Medical Microbiology, College of Science, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq
| | - Hala El-Haroun
- Basic Medical Science Department, Faculty of Dentistry, Al Ryada University for Science and Technology, Sadat City, Egypt
| | - Ahmed Mahal
- Department of Medical Biochemical Analysis, College of Health Technology, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq
| | - Lizaranee Tripathy
- Department of Chemistry, Centurion University of Technology and Management, Balangir, Odisha, India
| | - Rajashree Mishra
- Department of Chemistry, Centurion University of Technology and Management, Balangir, Odisha, India
| | - Muhammed Shabil
- University Center for Research and Development, Chandigarh University, Mohali, Punjab, India
| | - Fahad A. Alhumaydhi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Mahalaqua N. Khatib
- Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India
| | - Ganesh Bushi
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Debankur Dey
- Medical College and Hospital Kolkata, Kolkata, India
| | - Prakasini Satapathy
- Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Medical Laboratories Techniques Department, Al-Mustaqbal University, Hillah, Babil, Iraq
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Pooja Bansal
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, India
| | - Kiran Bhopte
- IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh, India
| | - Balvir S. Tomar
- Institute of Pediatric Gastroenterology and Hepatology, NIMS University, Jaipur, India
| | - Snehasish Mishra
- School of Biotechnology, KIIT Deemed University, Bhubaneswar, Odisha, India
| | - Mohammed Alissa
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Ranjan K. Mohapatra
- Department of Chemistry, Government College of Engineering, Keonjhar, Odisha, India
| | - Zeinhom M. El-Bahy
- Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
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Kobayashi J, Kanou K, Okura H, Akter TMST, Fukushi S, Matsuyama S. Biochemical analysis of packing and assembling heptad repeat motifs in the coronavirus spike protein trimer. mBio 2024; 15:e0120324. [PMID: 39440974 PMCID: PMC11559096 DOI: 10.1128/mbio.01203-24] [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: 04/22/2024] [Accepted: 08/20/2024] [Indexed: 10/25/2024] Open
Abstract
During a coronavirus infection, the spike protein undergoes sequential structural transitions triggered by its receptor and the host protease at the interface between the virus and cell membranes, thereby mediating membrane fusion. After receptor binding, the heptad repeat motif (HR1/HR2) within the viral spike protein bridges the viral and cellular membranes; however, the intermediate conformation adopted by the spike protein when drawing the viral and cellular membranes into close proximity remains unclear due to its transient and unstable nature. Here, we experimentally induced conformational changes in the spike protein of a murine coronavirus by incubating the virus with its receptor, followed by exposure to trypsin. We then treated the virus/receptor complex with proteinase K to probe the tightly packed core structure of the spike protein. The conformations of the spike protein were predicted from the sizes of the protease digestion products detected by western blot analysis. Upon receptor binding, two bands (each showing different reactivity with a fusion-inhibiting HR2-peptide) were detected; we propose that these bands correspond to the packed and unpacked HR1/HR2 motifs. After trypsin-mediated triggering, measurement of temperature and time dependency revealed that packing of the remaining unpacked HR1/HR2 motifs and assembly of three HR1 motifs in a trimer occur almost simultaneously. Thus, the trimeric spike protein adopts an asymmetric-unassembled conformation after receptor binding, followed by direct assembly into the post-fusion form triggered by the host protease. This biochemical study provides mechanistic insight into the previously unknown intermediate structure of the viral fusion protein.IMPORTANCEDuring infection by an enveloped virus, receptor binding triggers fusion between the cellular membrane and the virus envelope, enabling delivery of the viral genome to the cytoplasm. The viral spike protein mediates membrane fusion; however the molecular mechanism underlying this process is unclear. This is because using structural biology methods to track the transient conformational changes induced in the unstable spike trimer is challenging. Here, we harnessed the ability of protease enzymes to recognize subtle differences on protein surfaces, allowing us to detect structural differences in the spike protein before and after conformational changes. Differences in the size of the degradation products were analyzed by western blot analysis. The proposed model explaining the conformational changes presented herein is a plausible candidate that provides valuable insight into unanswered questions in the field of virology.
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Affiliation(s)
- Jun Kobayashi
- Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Tokyo, Japan
| | - Kazuhiko Kanou
- Department of Quality Assurance, Radiation Safety, and Information Management, National Institute of Infectious Diseases, Tokyo, Japan
| | - Hiyori Okura
- Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Tokyo, Japan
| | - Tahmina MST Akter
- Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Tokyo, Japan
| | - Shuetsu Fukushi
- Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan
| | - Shutoku Matsuyama
- Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Tokyo, Japan
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Islam MA, Pathak K, Saikia R, Pramanik P, Das A, Talukdar P, Shakya A, Ghosh SK, Singh UP, Bhat HR. An in-depth analysis of COVID-19 treatment: Present situation and prospects. Arch Pharm (Weinheim) 2024; 357:e2400307. [PMID: 39106224 DOI: 10.1002/ardp.202400307] [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: 04/24/2024] [Revised: 07/05/2024] [Accepted: 07/08/2024] [Indexed: 08/09/2024]
Abstract
Coronavirus disease 2019 (COVID-19) the most contagious infection caused by the unique type of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produced a global pandemic that wreaked havoc on the health-care system, resulting in high morbidity and mortality. Several methods were implemented to tackle the virus, including the repurposing of existing medications and the development of vaccinations. The purpose of this article is to provide a complete summary of the current state and future possibilities for COVID-19 therapies. We describe the many treatment classes, such as antivirals, immunomodulators, and monoclonal antibodies, that have been repurposed or developed to treat COVID-19. We also looked at the clinical evidence for these treatments, including findings from observational studies and randomized-controlled clinical trials, and highlighted the problems and limitations of the available evidence. Furthermore, we reviewed existing clinical trials and prospective COVID-19 therapeutic options, such as novel medication candidates and combination therapies. Finally, we discussed the long-term consequences of COVID-19 and the importance of ongoing research into the development of viable treatments. This review will help physicians, researchers, and policymakers to understand the prevention and mitigation of COVID-19.
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Affiliation(s)
- Md Ariful Islam
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Kalyani Pathak
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Riya Saikia
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Pallab Pramanik
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Aparoop Das
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Prasenjit Talukdar
- Department of Petroleum Engineering, DUIET, Dibrugarh, University, Assam, India
| | - Anshul Shakya
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Surajit Kumar Ghosh
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Udaya Pratap Singh
- Drug Design & Discovery Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India
| | - Hans Raj Bhat
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
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Tanrıverdi Ö, Alkan A, Karaoglu T, Kitaplı S, Yildiz A. COVID-19 and Carcinogenesis: Exploring the Hidden Links. Cureus 2024; 16:e68303. [PMID: 39350850 PMCID: PMC11441415 DOI: 10.7759/cureus.68303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2024] [Indexed: 10/04/2024] Open
Abstract
The COVID-19 pandemic caused by the SARS-CoV-2 virus has been studied predominantly in terms of its immediate respiratory and systemic effects. However, emerging evidence suggests possible long-term effects, including its role in carcinogenesis. This comprehensive review explores the complex relationship between COVID-19 and cancer development, focusing on immune dysregulation, chronic inflammation, genetic and epigenetic alterations, and the impact of therapeutic interventions. We also focused on the molecular mechanisms by which SARS-CoV-2 may facilitate cancer progression, including the roles of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and FURIN. Additionally, we examined the possible carcinogenic effects of long-term COVID-19 treatments and the interaction between co-infections and cancer risk. Our findings highlight the need for increased cancer surveillance in COVID-19 survivors. In the post-COVID-19 period, it can be thought that inflammation associated with excessive cytokine release, especially interleukin-6, genetic and epigenetic changes, and co-infections with oncogenic viruses such as Epstein-Barr virus or human papillomavirus may be effective in the development and progression of cancer. Further research is needed to explain the mechanisms underlying this relationship.
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Affiliation(s)
- Özgür Tanrıverdi
- Medical Oncology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
| | - Ali Alkan
- Medical Oncology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
| | | | - Sait Kitaplı
- Medical Oncology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
| | - Aysegul Yildiz
- Molecular Biology and Genetics, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
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Daniels A, Padariya M, Fletcher S, Ball K, Singh A, Carragher N, Hupp T, Tait-Burkard C, Kalathiya U. Molecules targeting a novel homotrimer cavity of Spike protein attenuate replication of SARS-CoV-2. Antiviral Res 2024; 228:105949. [PMID: 38942150 DOI: 10.1016/j.antiviral.2024.105949] [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: 02/20/2024] [Revised: 06/14/2024] [Accepted: 06/25/2024] [Indexed: 06/30/2024]
Abstract
The SARS-CoV-2 Spike glycoprotein (S) utilizes a unique trimeric conformation to interact with the ACE2 receptor on host cells, making it a prime target for inhibitors that block viral entry. We have previously identified a novel proteinaceous cavity within the Spike protein homotrimer that could serve as a binding site for small molecules. However, it is not known whether these molecules would inhibit, stimulate, or have no effect on viral replication. To address this, we employed structural-based screening to identify small molecules that dock into the trimer cavity and assessed their impact on viral replication. Our findings show that a cohort of identified small molecules binding to the Spike trimer cavity effectively reduces the replication of various SARS-CoV-2 variants. These molecules exhibited inhibitory effects on B.1 (European original, D614G, EDB2) and B.1.617.2 (δ) variants, while showing moderate activity against the B.1.1.7 (α) variant. We further categorized these molecules into distinct groups based on their structural similarities. Our experiments demonstrated a dose-dependent viral replication inhibitory activity of these compounds, with some, like BCC0040453 exhibiting no adverse effects on cell viability even at high concentrations. Further investigation revealed that pre-incubating virions with compounds like BCC0031216 at different temperatures significantly inhibited viral replication, suggesting their specificity towards the S protein. Overall, our study highlights the inhibitory impact of a diverse set of chemical molecules on the biological activity of the Spike protein. These findings provide valuable insights into the role of the trimer cavity in the viral replication cycle and aid drug discovery programs aimed at targeting the coronavirus family.
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Affiliation(s)
- Alison Daniels
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, United Kingdom
| | - Monikaben Padariya
- International Centre for Cancer Vaccine Science, University of Gdansk, ul. Kładki 24, 80-822 Gdańsk, Poland
| | - Sarah Fletcher
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, United Kingdom
| | - Kathryn Ball
- University of Edinburgh, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom
| | - Ashita Singh
- University of Edinburgh, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom
| | - Neil Carragher
- University of Edinburgh, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom
| | - Ted Hupp
- International Centre for Cancer Vaccine Science, University of Gdansk, ul. Kładki 24, 80-822 Gdańsk, Poland; University of Edinburgh, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom
| | - Christine Tait-Burkard
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, United Kingdom.
| | - Umesh Kalathiya
- International Centre for Cancer Vaccine Science, University of Gdansk, ul. Kładki 24, 80-822 Gdańsk, Poland.
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Wu G, Li Q, Dai J, Mao G, Ma Y. Design and Application of Biosafe Coronavirus Engineering Systems without Virulence. Viruses 2024; 16:659. [PMID: 38793541 PMCID: PMC11126016 DOI: 10.3390/v16050659] [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: 03/29/2024] [Revised: 04/15/2024] [Accepted: 04/18/2024] [Indexed: 05/26/2024] Open
Abstract
In the last twenty years, three deadly zoonotic coronaviruses (CoVs)-namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2-have emerged. They are considered highly pathogenic for humans, particularly SARS-CoV-2, which caused the 2019 CoV disease pandemic (COVID-19), endangering the lives and health of people globally and causing unpredictable economic losses. Experiments on wild-type viruses require biosafety level 3 or 4 laboratories (BSL-3 or BSL-4), which significantly hinders basic virological research. Therefore, the development of various biosafe CoV systems without virulence is urgently needed to meet the requirements of different research fields, such as antiviral and vaccine evaluation. This review aimed to comprehensively summarize the biosafety of CoV engineering systems. These systems combine virological foundations with synthetic genomics techniques, enabling the development of efficient tools for attenuated or non-virulent vaccines, the screening of antiviral drugs, and the investigation of the pathogenic mechanisms of novel microorganisms.
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Affiliation(s)
- Guoqiang Wu
- CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (G.W.); (Q.L.); (J.D.)
- School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau SAR 999078, China
| | - Qiaoyu Li
- CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (G.W.); (Q.L.); (J.D.)
- College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Junbiao Dai
- CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (G.W.); (Q.L.); (J.D.)
- Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China
| | - Guobin Mao
- CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (G.W.); (Q.L.); (J.D.)
| | - Yingxin Ma
- CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (G.W.); (Q.L.); (J.D.)
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Vajdi M, Karimi A, Hassanizadeh S, Farhangi MA, Bagherniya M, Askari G, Roufogalis BD, Davies NM, Sahebkar A. Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy. Pharmacol Rep 2024; 76:307-327. [PMID: 38498260 DOI: 10.1007/s43440-024-00585-6] [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: 09/23/2023] [Revised: 03/01/2024] [Accepted: 03/03/2024] [Indexed: 03/20/2024]
Abstract
The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic potential. Researchers have developed methods for separating and isolating polyphenols from complex matrices. Polyphenols are effective in treating common viral infections, including COVID-19, and can also boost immunity. Polyphenolic-based antiviral medications can mitigate SARS-CoV-2 enzymes vital to virus replication and infection. Individual polyphenolic triterpenoids, flavonoids, anthraquinonoids, and tannins may also inhibit the SARS-CoV-2 protease. Polyphenol pharmacophore structures identified to date can explain their action and lead to the design of novel anti-COVID-19 compounds. Polyphenol-containing mixtures offer the advantages of a well-recognized safety profile with few known severe side effects. However, studies to date are limited, and further animal studies and randomized controlled trials are needed in future studies. The purpose of this study was to review and present the latest findings on the therapeutic impact of plant-derived polyphenols on COVID-19 infection and its complications. Exploring alternative approaches to traditional therapies could aid in developing novel drugs and remedies against coronavirus infection.
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Affiliation(s)
- Mahdi Vajdi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Arash Karimi
- Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Shirin Hassanizadeh
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahdieh Abbasalizad Farhangi
- Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Bagherniya
- Department of Community Nutrition, Food Security Research Center, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Askari
- Department of Community Nutrition, Food Security Research Center, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Basil D Roufogalis
- Discipline of Pharmacology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia
- NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia
| | - Neal M Davies
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2P5, Canada
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Birtles D, Abbas W, Lee J. Bis(Monoacylglycero)Phosphate Promotes Membrane Fusion Facilitated by the SARS-CoV-2 Fusion Domain. J Phys Chem B 2024; 128:2675-2683. [PMID: 38466655 DOI: 10.1021/acs.jpcb.3c07863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/13/2024]
Abstract
Membrane fusion is a critical component of the viral lifecycle. For SARS-CoV-2, fusion is facilitated by the spike glycoprotein and can take place via either the plasma membrane or the endocytic pathway. The fusion domain (FD), which is found within the spike glycoprotein, is primarily responsible for the initiation of fusion as it embeds itself within the target cell's membrane. A preference for SARS-CoV-2 to fuse at low pH akin to the environment of the endocytic pathway has already been established; however, the impact of the target cell's lipid composition on the FD has yet to be explored. Here, we have shown that the SARS-CoV-2 FD preferentially initiates fusion at the late endosomal membrane over the plasma membrane, on the basis of lipid composition alone. A positive, fusogenic relationship with anionic lipids from the plasma membrane (POPS: 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine) and endosomal membrane (BMP: bis(monoacylglycero)phosphate) was established, with a large preference demonstrated for the latter. When comparing the binding affinity and secondary structure of the FD in the presence of different anionic lipids, little deviation was evident while the charge was maintained. However, it was discovered that BMP had a subtle, negative impact on lipid packing in comparison to that of POPS. Furthermore, an inverse relationship between lipid packing and the fusogenecity of the SARS-CoV-2 FD was witnessed. In conclusion, the SARS-CoV-2 FD preferentially initiates fusion at a membrane resembling that of the late endosomal compartment, predominately due to the presence of BMP and its impact on lipid packing.
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Affiliation(s)
- Daniel Birtles
- Department of Chemistry and Biochemistry, University of Maryland, College Park 20742, Maryland, United States
| | - Wafa Abbas
- Department of Chemistry and Biochemistry, University of Maryland, College Park 20742, Maryland, United States
| | - Jinwoo Lee
- Department of Chemistry and Biochemistry, University of Maryland, College Park 20742, Maryland, United States
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Takeda M. Cleavage-Activation of Respiratory Viruses - Half a Century of History from Sendai Virus to SARS-CoV-2. Jpn J Infect Dis 2024; 77:1-6. [PMID: 38030267 DOI: 10.7883/yoken.jjid.2023.353] [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] [Indexed: 12/01/2023]
Abstract
Many viruses require the cleavage-activation of membrane fusion proteins by host proteases in the course of infection. This knowledge is based on historical studies of Sendai virus in the 1970s. From the 1970s to the 1990s, avian influenza virus and Newcastle disease virus were studied, showing a clear link between virulence and the cleavage-activation of viral membrane fusion proteins (hemagglutinin and fusion proteins) by host proteases. In these viruses, cleavage of viral membrane fusion proteins by furin is the basis for their high virulence. Subsequently, from the 2000s to the 2010s, the importance of TMPRSS2 in activating the membrane fusion proteins of various respiratory viruses, including seasonal influenza viruses, was demonstrated. In late 2019, severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) emerged and caused a pandemic. The virus continues to mutate, producing variants that have caused global pandemics. The spike protein of SARS-CoV-2 is characterized by two cleavage sites, each of which is cleaved by furin and TMPRSS2 to achieve membrane fusion. SARS-CoV-2 variants exhibit altered sensitivity to these proteases. Thus, studying the cleavage-activation of membrane fusion proteins by host proteases is critical for understanding the ongoing pandemic and developing countermeasures against it.
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Affiliation(s)
- Makoto Takeda
- Department of Microbiology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan
- Pandemic Preparedness, Infection and Advanced Research Center, The University of Tokyo, Japan
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11
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Gasmi A, Noor S, Menzel A, Khanyk N, Semenova Y, Lysiuk R, Beley N, Bolibrukh L, Gasmi Benahmed A, Storchylo O, Bjørklund G. Potential Drugs in COVID-19 Management. Curr Med Chem 2024; 31:3245-3264. [PMID: 37461346 DOI: 10.2174/0929867331666230717154101] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 05/27/2023] [Accepted: 06/05/2023] [Indexed: 11/18/2023]
Abstract
The SARS-CoV-2 virus first emerged in China in December 2019 and quickly spread worldwide. Despite the absence of a vaccination or authorized drug specifically developed to combat this infection, certain medications recommended for other diseases have shown potential effectiveness in treating COVID-19, although without definitive confirmation. This review aims to evaluate the existing literature on the efficacy of these medications against COVID-19. The review encompasses various potential treatments, including antiviral medications, anti-malaria and anti-rheumatic drugs, vaccines, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), antipyretic and analgesic medicines, antiparasitic drugs, and statins. The analysis also addresses the potential benefits and drawbacks of these medications, as well as their effects on hypertension and diabetes. Although these therapies hold promise against COVID-19, further research, including suitable product production or clinical testing, is needed to establish their therapeutic efficacy.
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Affiliation(s)
- Amin Gasmi
- Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
| | - Sadaf Noor
- Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan
| | | | - Nataliia Khanyk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
- CONEM Ukraine Life Science Research Group, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Yuliya Semenova
- Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Roman Lysiuk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
- CONEM Ukraine Life Science Research Group, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Nataliya Beley
- I. Ya. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
| | | | | | - Olha Storchylo
- Medical Chemistry Department, Odessa National Medical University, Odesa, Ukraine
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway
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12
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Wu M, Li W, Lin S, Fan J, Cui L, Xiang Y, Li K, Tang L, Duan Y, Chen Z, Yang F, Shui W, Lu G, Lai Y. A Suitable Membrane Distance Regulated by the RBD_ACE2 Interaction is Critical for SARS-CoV-2 Spike-Mediated Viral Invasion. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2301478. [PMID: 37590389 PMCID: PMC10558659 DOI: 10.1002/advs.202301478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 06/25/2023] [Indexed: 08/19/2023]
Abstract
The receptor-binding domain (RBD) of spike recognizing the receptor angiotensin-converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell-vesicle content-mixing assay, it is found that the cleavage at the S2' site by thrombin (Thr) protease strongly accelerates membrane fusion, compared to that of cleavage at the S1/S2 site by PreScission (3C) protease. Moreover, mutations at the RBD_ACE2 interface resulted in a positive correlation between binding affinity and fusion probability. In both the cell-vesicle and cell-cell fusion assays, by crosslinking two membranes via the neutravidin (NTV)_biotin interaction or complementary DNA strands, it is found that spike drives membrane fusion in the absence of ACE2, and a suitable distance between two membranes is critical for spike-mediated membrane fusion. Finally, unsuitable membrane crosslinkers significantly inhibited the fusion probability in the presence of ACE2. Taken together, the results suggest that the RBD_ACE2 complex may act as a crosslinker to bridge the viral and cell membranes at a suitable distance, which is critical, but also substitutable for spike-mediated SARS-CoV-2 entry.
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Affiliation(s)
- Mengdan Wu
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Wei Li
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Sheng Lin
- West China Hospital Emergency DepartmentState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Jiaqi Fan
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Lele Cui
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Yijuan Xiang
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Kaiyu Li
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Linwei Tang
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Yanping Duan
- West China Hospital Emergency DepartmentState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Zimin Chen
- West China Hospital Emergency DepartmentState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Fanli Yang
- West China Hospital Emergency DepartmentState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Weiwei Shui
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Guangwen Lu
- West China Hospital Emergency DepartmentState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Ying Lai
- National Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China
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Wells EW, Parker MT. Regulating Select Agent Chimeras: Defining the Problem(s) Through the Lens of SARS-CoV-1/SARS-CoV-2 Chimeric Viruses. Health Secur 2023; 21:392-406. [PMID: 37703547 DOI: 10.1089/hs.2023.0008] [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] [Indexed: 09/15/2023] Open
Abstract
In late 2021, the US Centers for Disease Control and Prevention (CDC) posted an interim final rule (86 FR 64075) to the federal register regulating the possession, use, and transfer of SARS-CoV-1/SARS-CoV-2 chimeric viruses. In doing so, the CDC provided the reasoning that viral chimeras combining the transmissibility of SARS-CoV-2 with the pathogenicity and lethality of SARS-CoV-1 pose a significant risk to public health and should thus be placed on the select agents and toxins list. However, 86 FR 64075 lacked clarity in its definitions and scope, some of which the CDC addressed in response to public comments in the final rule, 88 FR 13322, in early 2023. To evaluate these regulatory actions, we reviewed the existing select agent regulations to understand the landscape of chimeric virus regulation. Based on our findings, we first present clear definitions for the terms "chimeric virus," "viral chimera," and "virulence factor" and provide a list of SARS-CoV-1 virulence factors in an effort to aid researchers and federal rulemaking for these agents moving forward. We then provide suggestions for a combination of similarity and functional characteristic cutoffs that the government could use to enable researchers to distinguish between regulated and nonregulated chimeras. Finally, we discuss current select agent regulations and their overlaps with 86 FR 64075 and 88 FR 13322 and make suggestions for how to address chimera concerns within and/or without these regulations. Collectively, we believe that our findings fill important gaps in current federal regulations and provide forward-looking philosophical and practical analysis that can guide future decisionmaking.
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Affiliation(s)
- Elizabeth W Wells
- Elizabeth W. Wells is a Student, Department of Biology, Georgetown College of Arts & Sciences, Georgetown University, Washington, DC
| | - Michael T Parker
- Michael T. Parker, PhD, is Assistant Dean, Georgetown College of Arts & Sciences, Georgetown University, Washington, DC
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14
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Bisen AC, Agrawal S, Sanap SN, Ravi Kumar HG, Kumar N, Gupta R, Bhatta RS. COVID-19 retreats and world recovers: A silver lining in the dark cloud. HEALTH CARE SCIENCE 2023; 2:264-285. [PMID: 38939523 PMCID: PMC11080794 DOI: 10.1002/hcs2.57] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/30/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2024]
Abstract
The coronavirus disease (COVID-19), which the World Health Organization classified as the Sixth Public Health Emergency Of International Concern (PHEIC) on January 30, 2020, is no longer a PHEIC. Millions were affected due to unawareness. The increase in fatalities and shortage of medicine was the first outrage of COVID-19. As per the Johns Hopkins COVID-19 resource center database, it was observed that the disease has spread dynamically across 200+ nations worldwide affecting more than 600 million people from 2019 to 2023, and over thousands of people were victimized regularly at a 2% mortality rate (approx.). In the midway, the mutant variants of concern like omicron, and delta have also created havoc and caused significant impact on public health, global economy, and lifestyle. Since 2019, 3 years now passed and the dynamic disease statistics seem decelerated; moreover, the prevalence of COVID-19 is also fading. The Johns Hopkins resource center has also stopped recording the data of the global pandemic recently from March 10, 2023. Hence, based on the facts, we are presenting a concise report on the pandemic from 2019 to 2023, which includes a brief discussion of the global pandemic. We have highlighted global epidemiology, emphasizing the Indian COVID scenario, vaccination across the globe, and the psychosocial and geopolitical consequences of COVID-19 with a brief background to pathology, clinical management, and the worldwide response against triage. A lot has changed and still needs to change after three tough years of COVID-19. Even though science has progressed and advanced research in medicine is pointing toward future generations, there is no standard care supplied for COVID-19-like calamities. COVID-19 cases might have declined but its influence on the society is still stagnant. This COVID experience has taught us that, despite our bleak beginnings, there is always hope for the future and that we must act with foresight to improve things for future generations.
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Affiliation(s)
- Amol Chhatrapati Bisen
- Pharmaceutics and Pharmacokinetics DivisionCSIR—Central Drug Research InstituteLucknowUttar PradeshIndia
- Academy of Scientific and Innovative Research (AcSIR)GhaziabadUttar PradeshIndia
| | - Sristi Agrawal
- Pharmaceutics and Pharmacokinetics DivisionCSIR—Central Drug Research InstituteLucknowUttar PradeshIndia
- Academy of Scientific and Innovative Research (AcSIR)GhaziabadUttar PradeshIndia
| | - Sachin Nashik Sanap
- Pharmaceutics and Pharmacokinetics DivisionCSIR—Central Drug Research InstituteLucknowUttar PradeshIndia
- Academy of Scientific and Innovative Research (AcSIR)GhaziabadUttar PradeshIndia
| | | | - Nelam Kumar
- Biochemistry and Structural Biology DivisionCSIR—Central Drug Research InstituteLucknowUttar PradeshIndia
- Present address:
International Centre for Translational Eye Research (ICTER)Institute of Physical Chemistry (IChF)Marcina Kasprzaka 44/5201‐224WarsawPoland
| | - Rajdeep Gupta
- Pharmaceutics and Pharmacokinetics DivisionCSIR—Central Drug Research InstituteLucknowUttar PradeshIndia
| | - Rabi Sankar Bhatta
- Pharmaceutics and Pharmacokinetics DivisionCSIR—Central Drug Research InstituteLucknowUttar PradeshIndia
- Academy of Scientific and Innovative Research (AcSIR)GhaziabadUttar PradeshIndia
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15
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Zhang P, Falcone S, Tsybovsky Y, Singh M, Gopan V, Miao H, Seo Y, Rogers D, Renzi I, Lai YT, Narayanan E, Stewart-Jones G, Himansu S, Carfi A, Fauci AS, Lusso P. Increased neutralization potency and breadth elicited by a SARS-CoV-2 mRNA vaccine forming virus-like particles. Proc Natl Acad Sci U S A 2023; 120:e2305896120. [PMID: 37428933 PMCID: PMC10629519 DOI: 10.1073/pnas.2305896120] [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: 04/13/2023] [Accepted: 05/26/2023] [Indexed: 07/12/2023] Open
Abstract
Vaccines have played a fundamental role in the control of infectious diseases. We previously developed a messenger RNA (mRNA) vaccine against HIV-1 that forms virus-like particles (VLPs) through coexpression of the viral envelope with Gag. Here, we applied the same principle to the design of a VLP-forming mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To promote cognate interaction with simian immunodeficiency virus (SIV) Gag, we engineered different chimeric proteins encompassing the ectodomain and the transmembrane region of the SARS-CoV-2 Spike protein from the Wuhan-Hu-1 strain fused to the gp41 cytoplasmic tail of either HIV-1 (strain WITO) or SIV (strain mac239) with or without a partial truncation at amino acid 745 to enhance membrane expression. Upon cotransfection with SIV gag mRNA, the Spike-SIVCT.745 (SSt) chimera yielded the highest level of cell-surface expression and extracellular VLP release. Immunization of BALB/c mice with SSt+gag mRNA at 0, 4, and 16 wk induced higher titers of Spike-binding and autologous neutralizing antibodies at all time points compared to SSt mRNA alone. Furthermore, mice immunized with SSt+gag mRNA developed neutralizing antibodies effective against different variants of concern. These data demonstrate that the Gag/VLP mRNA platform can be successfully applied to vaccines against different agents for the prevention of infectious diseases of global relevance.
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Affiliation(s)
- Peng Zhang
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
| | | | - Yaroslav Tsybovsky
- Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD21703
| | - Mamta Singh
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
| | - Vinay Gopan
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
| | - Huiyi Miao
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
| | - Yuna Seo
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
| | - Denise Rogers
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
| | | | | | | | | | | | | | - Anthony S. Fauci
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
| | - Paolo Lusso
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD20892
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16
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Giron CC, Laaksonen A, Barroso da Silva FL. Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies. J Biomol Struct Dyn 2023; 41:5707-5727. [PMID: 35815535 DOI: 10.1080/07391102.2022.2095305] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 06/23/2022] [Indexed: 12/23/2022]
Abstract
SARS-CoV-2 remains a health threat with the continuous emergence of new variants. This work aims to expand the knowledge about the SARS-CoV-2 receptor-binding domain (RBD) interactions with cell receptors and monoclonal antibodies (mAbs). By using constant-pH Monte Carlo simulations, the free energy of interactions between the RBD from different variants and several partners (Angiotensin-Converting Enzyme-2 (ACE2) polymorphisms and various mAbs) were predicted. Computed RBD-ACE2-binding affinities were higher for two ACE2 polymorphisms (rs142984500 and rs4646116) typically found in Europeans which indicates a genetic susceptibility. This is amplified for Omicron (BA.1) and its sublineages BA.2 and BA.3. The antibody landscape was computationally investigated with the largest set of mAbs so far in the literature. From the 32 studied binders, groups of mAbs were identified from weak to strong binding affinities (e.g. S2K146). These mAbs with strong binding capacity and especially their combination are amenable to experimentation and clinical trials because of their high predicted binding affinities and possible neutralization potential for current known virus mutations and a universal coronavirus.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Carolina Corrêa Giron
- Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
- Universidade Federal do Triângulo Mineiro, Hospital de Clínicas, Uberaba, MG, Brazil
| | - Aatto Laaksonen
- Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden
- State Key Laboratory of Materials-Oriented and Chemical Engineering, Nanjing Tech University, Nanjing, PR China
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, Petru Poni Institute of Macromolecular Chemistry, Iasi, Romania
- Department of Engineering Sciences and Mathematics, Division of Energy Science, Luleå University of Technology, Luleå, Sweden
- Department of Chemical and Geological Sciences, University of Cagliari, Monserrato, Italy
| | - Fernando Luís Barroso da Silva
- Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
- Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA
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17
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von Delft A, Hall MD, Kwong AD, Purcell LA, Saikatendu KS, Schmitz U, Tallarico JA, Lee AA. Accelerating antiviral drug discovery: lessons from COVID-19. Nat Rev Drug Discov 2023; 22:585-603. [PMID: 37173515 PMCID: PMC10176316 DOI: 10.1038/s41573-023-00692-8] [Citation(s) in RCA: 79] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2023] [Indexed: 05/15/2023]
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, a wave of rapid and collaborative drug discovery efforts took place in academia and industry, culminating in several therapeutics being discovered, approved and deployed in a 2-year time frame. This article summarizes the collective experience of several pharmaceutical companies and academic collaborations that were active in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral discovery. We outline our opinions and experiences on key stages in the small-molecule drug discovery process: target selection, medicinal chemistry, antiviral assays, animal efficacy and attempts to pre-empt resistance. We propose strategies that could accelerate future efforts and argue that a key bottleneck is the lack of quality chemical probes around understudied viral targets, which would serve as a starting point for drug discovery. Considering the small size of the viral proteome, comprehensively building an arsenal of probes for proteins in viruses of pandemic concern is a worthwhile and tractable challenge for the community.
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Affiliation(s)
- Annette von Delft
- Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
- Oxford Biomedical Research Centre, National Institute for Health Research, University of Oxford, Oxford, UK.
| | - Matthew D Hall
- National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA
| | | | | | | | | | | | - Alpha A Lee
- PostEra, Inc., Cambridge, MA, USA.
- Cavendish Laboratory, University of Cambridge, Cambridge, UK.
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18
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Li Y, Shen Y, Zhang Y, Yan R. Structural Basis for the Enhanced Infectivity and Immune Evasion of Omicron Subvariants. Viruses 2023; 15:1398. [PMID: 37376697 PMCID: PMC10304477 DOI: 10.3390/v15061398] [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: 05/13/2023] [Revised: 06/08/2023] [Accepted: 06/18/2023] [Indexed: 06/29/2023] Open
Abstract
The Omicron variants of SARS-CoV-2 have emerged as the dominant strains worldwide, causing the COVID-19 pandemic. Each Omicron subvariant contains at least 30 mutations on the spike protein (S protein) compared to the original wild-type (WT) strain. Here we report the cryo-EM structures of the trimeric S proteins from the BA.1, BA.2, BA.3, and BA.4/BA.5 subvariants, with BA.4 and BA.5 sharing the same S protein mutations, each in complex with the surface receptor ACE2. All three receptor-binding domains of the S protein from BA.2 and BA.4/BA.5 are "up", while the BA.1 S protein has two "up" and one "down". The BA.3 S protein displays increased heterogeneity, with the majority in the all "up" RBD state. The different conformations preferences of the S protein are consistent with their varied transmissibility. By analyzing the position of the glycan modification on Asn343, which is located at the S309 epitopes, we have uncovered the underlying immune evasion mechanism of the Omicron subvariants. Our findings provide a molecular basis of high infectivity and immune evasion of Omicron subvariants, thereby offering insights into potential therapeutic interventions against SARS-CoV-2 variants.
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Affiliation(s)
- Yaning Li
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China
- Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Yaping Shen
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China
| | - Yuanyuan Zhang
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China
| | - Renhong Yan
- Key University Laboratory of Metabolism and Health of Guangdong, Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China
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19
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Qiu R, Chen F, Álvarez Z, Clemons TD, Biswas S, Karver MR, Takata N, Sai H, Peng H, Weigand S, Palmer LC, Stupp SI. Supramolecular Nanofibers Block SARS-CoV-2 Entry into Human Host Cells. ACS APPLIED MATERIALS & INTERFACES 2023; 15:26340-26348. [PMID: 37235485 DOI: 10.1021/acsami.3c02447] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) on host cells to initiate cellular entry. Blocking the interactions between the spike protein and ACE2 offers promising therapeutic opportunities to prevent infection. We report here on peptide amphiphile supramolecular nanofibers that display a sequence from ACE2 in order to promote interactions with the SARS-CoV-2 spike receptor binding domain. We demonstrate that displaying this sequence on the surface of supramolecular assemblies preserves its α-helical conformation and blocks the entry of a pseudovirus and its two variants into human host cells. We also found that the chemical stability of the bioactive structures was enhanced in the supramolecular environment relative to the unassembled peptide molecules. These findings reveal unique advantages of supramolecular peptide therapies to prevent viral infections and more broadly for other targets as well.
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Affiliation(s)
- Ruomeng Qiu
- Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
| | - Feng Chen
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
| | - Zaida Álvarez
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
- Department of Medicine, Northwestern University, 676 N. St. Clair Street, Chicago, Illinois 60611, United States
| | - Tristan D Clemons
- Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
| | - Suvendu Biswas
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
| | - Mark R Karver
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
| | - Nozomu Takata
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
| | - Hiroaki Sai
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
- Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, Illinois 60208, United States
| | - Han Peng
- Department of Dermatology, Northwestern University, 303 E. Superior Street, Chicago, Illinois 60611, United States
| | - Steven Weigand
- DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) Synchrotron Research Center, Advanced Photon Source (APS)/Argonne National Laboratory 432-A004, Northwestern University, 9700 South Cass Avenue, Argonne, Illinois 60439, United States
| | - Liam C Palmer
- Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
| | - Samuel I Stupp
- Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
- Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, Illinois 60208, United States
- Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
- Department of Medicine, Northwestern University, 676 N. St. Clair Street, Chicago, Illinois 60611, United States
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Sengar A, Cervantes M, Bondalapati ST, Hess T, Kasson PM. Single-Virus Fusion Measurements Reveal Multiple Mechanistically Equivalent Pathways for SARS-CoV-2 Entry. J Virol 2023; 97:e0199222. [PMID: 37133381 PMCID: PMC10231210 DOI: 10.1128/jvi.01992-22] [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: 01/05/2023] [Accepted: 04/11/2023] [Indexed: 05/04/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to cell surface receptors and is activated for membrane fusion and cell entry via proteolytic cleavage. Phenomenological data have shown that SARS-CoV-2 can be activated for entry at either the cell surface or in endosomes, but the relative roles in different cell types and mechanisms of entry have been debated. Here, we used single-virus fusion experiments and exogenously controlled proteases to probe activation directly. We found that plasma membrane and an appropriate protease are sufficient to support SARS-CoV-2 pseudovirus fusion. Furthermore, fusion kinetics of SARS-CoV-2 pseudoviruses are indistinguishable no matter which of a broad range of proteases is used to activate the virus. This suggests that the fusion mechanism is insensitive to protease identity or even whether activation occurs before or after receptor binding. These data support a model for opportunistic fusion by SARS-CoV-2 in which the subcellular location of entry likely depends on the differential activity of airway, cellsurface, and endosomal proteases, but all support infection. Inhibition of any single host protease may thus reduce infection in some cells but may be less clinically robust. IMPORTANCE SARS-CoV-2 can use multiple pathways to infect cells, as demonstrated recently when new viral variants switched dominant infection pathways. Here, we used single-virus fusion experiments together with biochemical reconstitution to show that these multiple pathways coexist simultaneously and specifically that the virus can be activated by different proteases in different cellular compartments with mechanistically identical effects. The consequences of this are that the virus is evolutionarily plastic and that therapies targeting viral entry should address multiple pathways at once to achieve optimal clinical effects.
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Affiliation(s)
- Anjali Sengar
- Department of Molecular Physiology, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
- Department of Biomedical Engineering, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
| | - Marcos Cervantes
- Department of Molecular Physiology, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
- Department of Biomedical Engineering, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
| | - Sai T. Bondalapati
- Department of Molecular Physiology, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
- Department of Biomedical Engineering, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
| | - Tobin Hess
- Department of Molecular Physiology, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
- Department of Biomedical Engineering, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
| | - Peter M. Kasson
- Department of Molecular Physiology, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
- Department of Biomedical Engineering, Global Infectious Diseases Institute, University of Virginia, Charlottesville, Virginia, USA
- Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
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21
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Tian WJ, Wang XJ. Broad-Spectrum Antivirals Derived from Natural Products. Viruses 2023; 15:v15051100. [PMID: 37243186 DOI: 10.3390/v15051100] [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: 03/09/2023] [Revised: 04/26/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023] Open
Abstract
Scientific advances have led to the development and production of numerous vaccines and antiviral drugs, but viruses, including re-emerging and emerging viruses, such as SARS-CoV-2, remain a major threat to human health. Many antiviral agents are rarely used in clinical treatment, however, because of their inefficacy and resistance. The toxicity of natural products may be lower, and some natural products have multiple targets, which means less resistance. Therefore, natural products may be an effective means to solve virus infection in the future. New techniques and ideas are currently being developed for the design and screening of antiviral drugs thanks to recent revelations about virus replication mechanisms and the advancement of molecular docking technology. This review will summarize recently discovered antiviral drugs, mechanisms of action, and screening and design strategies for novel antiviral agents.
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Affiliation(s)
- Wen-Jun Tian
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, China Agricultural University, Beijing 100193, China
| | - Xiao-Jia Wang
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, China Agricultural University, Beijing 100193, China
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22
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Castillo G, Mora-Díaz JC, Breuer M, Singh P, Nelli RK, Giménez-Lirola LG. Molecular mechanisms of human coronavirus NL63 infection and replication. Virus Res 2023; 327:199078. [PMID: 36813239 PMCID: PMC9944649 DOI: 10.1016/j.virusres.2023.199078] [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: 12/20/2022] [Revised: 02/16/2023] [Accepted: 02/17/2023] [Indexed: 02/24/2023]
Abstract
Human coronavirus NL63 (HCoV-NL63) is spread globally, causing upper and lower respiratory tract infections mainly in young children. HCoV-NL63 shares a host receptor (ACE2) with severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 but, unlike them, HCoV-NL63 primarily develops into self-limiting mild to moderate respiratory disease. Although with different efficiency, both HCoV-NL63 and SARS-like CoVs infect ciliated respiratory cells using ACE2 as receptor for binding and cell entry. Working with SARS-like CoVs require access to BSL-3 facilities, while HCoV-NL63 research can be performed at BSL-2 laboratories. Thus, HCoV-NL63 could be used as a safer surrogate for comparative studies on receptor dynamics, infectivity and virus replication, disease mechanism, and potential therapeutic interventions against SARS-like CoVs. This prompted us to review the current knowledge on the infection mechanism and replication of HCoV-NL63. Specifically, after a brief overview on the taxonomy, genomic organization and virus structure, this review compiles the current HCoV-NL63-related research in virus entry and replication mechanism, including virus attachment, endocytosis, genome translation, and replication and transcription. Furthermore, we reviewed cumulative knowledge on the susceptibility of different cells to HCoV-NL63 infection in vitro, which is essential for successful virus isolation and propagation, and contribute to address different scientific questions from basic science to the development and assessment of diagnostic tools, and antiviral therapies. Finally, we discussed different antiviral strategies that have been explored to suppress replication of HCoV-NL63, and other related human coronaviruses, by either targeting the virus or enhancing host antiviral mechanisms.
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Affiliation(s)
- Gino Castillo
- Department of Veterinary Diagnostic and Production Animal Medicine, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011, USA
| | - Juan Carlos Mora-Díaz
- Department of Veterinary Diagnostic and Production Animal Medicine, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011, USA
| | - Mary Breuer
- Department of Veterinary Diagnostic and Production Animal Medicine, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011, USA
| | - Pallavi Singh
- Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115, USA
| | - Rahul K Nelli
- Department of Veterinary Diagnostic and Production Animal Medicine, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011, USA
| | - Luis G Giménez-Lirola
- Department of Veterinary Diagnostic and Production Animal Medicine, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011, USA.
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23
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Lukiw WJ, Pogue AI. Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain. Int J Mol Sci 2023; 24:3363. [PMID: 36834773 PMCID: PMC9966119 DOI: 10.3390/ijms24043363] [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: 12/27/2022] [Revised: 02/03/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5'-methyl cap (m7GpppN), a 3'- and 5'-untranslated region (3'-UTR, 5'-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body's natural complement of about ~2650 miRNA species. Depending on host cell and tissue type, in silico analysis, RNA sequencing, and molecular-genetic investigations indicate that, remarkably, almost every single human miRNA has the potential to interact with the primary sequence of SARS-CoV-2 ssvRNA. Individual human variation in host miRNA abundance, speciation, and complexity among different human populations and additional variability in the cell and tissue distribution of the SARS-CoV-2 angiotensin converting enzyme-2 (ACE2) receptor (ACE2R) appear to further contribute to the molecular-genetic basis for the wide variation in individual host cell and tissue susceptibility to COVID-19 infection. In this paper, we review recently described aspects of the miRNA and ssvRNA ribonucleotide sequence structure in this highly evolved miRNA-ssvRNA recognition and signaling system and, for the first time, report the most abundant miRNAs in the control superior temporal lobe neocortex (STLN), an anatomical area involved in cognition and targeted by both SARS-CoV-2 invasion and Alzheimer's disease (AD). We further evaluate important factors involving the neurotropic nature of SARS-CoV-2 and miRNAs and ACE2R distribution in the STLN that modulate significant functional deficits in the brain and CNS associated with SARS-CoV-2 infection and COVID-19's long-term neurological effects.
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Affiliation(s)
- Walter J. Lukiw
- LSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USA
- Alchem Biotech Research, Toronto, ON M5S 1A8, Canada
- Department of Ophthalmology, LSU Health Science Center, New Orleans, LA 70112, USA
- Department Neurology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA
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24
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Budak C, Mençik V, Gider V. Determining similarities of COVID-19 - lung cancer drugs and affinity binding mode analysis by graph neural network-based GEFA method. J Biomol Struct Dyn 2023; 41:659-671. [PMID: 34877907 DOI: 10.1080/07391102.2021.2010601] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
COVID-19 is a worldwide health crisis seriously endangering the arsenal of antiviral and antibiotic drugs. It is urgent to find an effective antiviral drug against pandemic caused by the severe acute respiratory syndrome (Sars-Cov-2), which increases global health concerns. As it can be expensive and time-consuming to develop specific antiviral drugs, reuse of FDA-approved drugs that provide an opportunity to rapidly distribute effective therapeutics can allow to provide treatments with known preclinical, pharmacokinetic, pharmacodynamic and toxicity profiles that can quickly enter in clinical trials. In this study, using the structural information of molecules and proteins, a list of repurposed drug candidates was prepared again with the graph neural network-based GEFA model. The data set from the public databases DrugBank and PubChem were used for analysis. Using the Tanimoto/jaccard similarity analysis, a list of similar drugs was prepared by comparing the drugs used in the treatment of COVID-19 with the drugs used in the treatment of other diseases. The resultant drugs were compared with the drugs used in lung cancer and repurposed drugs were obtained again by calculating the binding strength between a drug and a target. The kinase inhibitors (erlotinib, lapatinib, vandetanib, pazopanib, cediranib, dasatinib, linifanib and tozasertib) obtained from the study can be used as an alternative for the treatment of COVID-19, as a combination of blocking agents (gefitinib, osimertinib, fedratinib, baricitinib, imatinib, sunitinib and ponatinib) such as ABL2, ABL1, EGFR, AAK1, FLT3 and JAK1, or antiviral therapies (ribavirin, ritonavir-lopinavir and remdesivir).Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Cafer Budak
- Department of Biomedical Engineering, Dicle University, Diyarbakır, Turkey
| | - Vasfiye Mençik
- Department of Electric-Electronic Engineering, Dicle University, Diyarbakır, Turkey
| | - Veysel Gider
- Department of Electric-Electronic Engineering, Dicle University, Diyarbakır, Turkey
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25
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He W, Shi X, Guan H, Zou Y, Zhang S, Jiang Z, Su S. Identification of a novel linear B-cell epitope in porcine deltacoronavirus nucleocapsid protein. Appl Microbiol Biotechnol 2023; 107:651-661. [PMID: 36602561 PMCID: PMC9813470 DOI: 10.1007/s00253-022-12348-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 11/29/2022] [Accepted: 12/22/2022] [Indexed: 01/06/2023]
Abstract
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus that caused diarrhea and/or vomiting in neonatal piglets worldwide. Coronaviruses nucleocapsid (N) protein is the most conserved structural protein for viral replication and possesses good antigenicity. In this study, three monoclonal antibodies (mAbs), 3B4, 4D3, and 4E3 identified as subclass IgG2aκ were prepared using the lymphocytic hybridoma technology against PDCoV N protein. Furthermore, the B-cell epitope recognized by mAb 4D3 was mapped by dozens of overlapping truncated recombinant proteins based on the western blotting. The polypeptide 28QFRGNGVPLNSAIKPVE44 (EP-4D3) in the N-terminal of PDCoV N protein was identified as the minimal linear epitope for binding mAb 4D3. And the EP-4D3 epitope's amino acid sequence homology study revealed that PDCoV strains are substantially conserved, with the exception of the Alanine43 substitution Valine43 in the China lineage, the Early China lineage, and the Thailand, Vietnam, and Laos lineage. The epitope sequences shared high similarity (94.1%) with porcine coronavirus HKU15-155 (PorCoV HKU15), Asian leopard cats coronavirus (ALCCoV), sparrow coronavirus HKU17 (SpCoV HKU17), and sparrow deltacoronavirus. In contrast, the epitope sequences shared a very low homology (11.8 to 29.4%) with other porcine CoVs (PEDV, TGEV, PRCV, SADS-CoV, PHEV). Overall, the study will enrich the biological function of PDCoV N protein and provide foundational data for further development of diagnostic applications. KEY POINTS: • Three monoclonal antibodies against PDCoV N protein were prepared. • Discovery of a novel B-cell liner epitope (28QFRGNGVPLNSAIKPVE44) of PDCoV N protein. • The epitope EP-4D3 was conserved among PDCoV strains.
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Affiliation(s)
- Wei He
- Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
- Sanya Institute of Nanjing Agricultural University, Sanya, China
| | - Xinze Shi
- Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
| | - Haifei Guan
- Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
| | - Yuntong Zou
- Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
| | - Shengkun Zhang
- Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
| | - Zhiwen Jiang
- Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
| | - Shuo Su
- Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
- Sanya Institute of Nanjing Agricultural University, Sanya, China.
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26
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Production and characterization of lentivirus vector-based SARS-CoV-2 pseudoviruses with dual reporters: Evaluation of anti-SARS-CoV-2 viral effect of Korean Red Ginseng. J Ginseng Res 2023; 47:123-132. [PMID: 35855181 PMCID: PMC9283196 DOI: 10.1016/j.jgr.2022.07.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 01/09/2023] Open
Abstract
Background Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean Red Ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus. Methods A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2. Results The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect. Conclusion The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.
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27
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Papageorgiou L, Papakonstantinou E, Diakou I, Pierouli K, Dragoumani K, Bacopoulou F, Chrousos GP, Eliopoulos E, Vlachakis D. Semantic and Population Analysis of the Genetic Targets Related to COVID-19 and Its Association with Genes and Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1423:59-78. [PMID: 37525033 DOI: 10.1007/978-3-031-31978-5_6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
SARS-CoV-2 is a coronavirus responsible for one of the most serious, modern worldwide pandemics, with lasting and multifaceted effects. By late 2021, SARS-CoV-2 has infected more than 180 million people and has killed more than 3 million. The virus gains entrance to human cells through binding to ACE2 via its surface spike protein and causes a complex disease of the respiratory system, termed COVID-19. Vaccination efforts are being made to hinder the viral spread, and therapeutics are currently under development. Toward this goal, scientific attention is shifting toward variants and SNPs that affect factors of the disease such as susceptibility and severity. This genomic grammar, tightly related to the dark part of our genome, can be explored through the use of modern methods such as natural language processing. We present a semantic analysis of SARS-CoV-2-related publications, which yielded a repertoire of SNPs, genes, and disease ontologies. Population data from the 1000 Genomes Project were subsequently integrated into the pipeline. Data mining approaches of this scale have the potential to elucidate the complex interaction between COVID-19 pathogenesis and host genetic variation; the resulting knowledge can facilitate the management of high-risk groups and aid the efforts toward precision medicine.
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Affiliation(s)
- Louis Papageorgiou
- Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
| | - Eleni Papakonstantinou
- Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
| | - Io Diakou
- Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
| | - Katerina Pierouli
- Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
| | - Konstantina Dragoumani
- Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
| | - Flora Bacopoulou
- University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece
| | - George P Chrousos
- University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece
| | - Elias Eliopoulos
- Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
| | - Dimitrios Vlachakis
- Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece.
- University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece.
- Division of Endocrinology and Metabolism, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
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28
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Characterization of SARS-CoV-2 Glycoprotein Using a Quantitative Cell-Cell Fusion System. Methods Mol Biol 2022; 2610:179-186. [PMID: 36534291 DOI: 10.1007/978-1-0716-2895-9_15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Coronaviruses (CoVs) infect host cells through the fusion of viral and cellular membrane and may also spread to the neighboring uninfected cells from infected cells through cell-cell fusion. The viral spike (S) glycoproteins play an essential role in mediating membrane fusion. Here, we present a luciferase-based quantitative assay to measure the efficiency of cell-cell fusion mediated by the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This method applies to S proteins of the other coronaviruses and can be adapted to fusion proteins of other enveloped viruses.
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29
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A Lentiviral Pseudotype System to Characterize SARS-CoV-2 Glycoprotein. Methods Mol Biol 2022; 2610:187-199. [PMID: 36534292 DOI: 10.1007/978-1-0716-2895-9_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 causes worldwide COVID-19 pandemic and poses a great threat to global public health. Due to its high pathogenicity and infectivity, live SARS-CoV-2 is classified as a BSL-3 agent and has to be handled in BSL-3 condition. Nevertheless, entry of SARS-CoV-2 is mediated by viral spike (S) glycoprotein, and pseudovirus with SARS-CoV-2 S protein can mimic every entry step of SARS-CoV-2 virus and be studied in BSL-2 settings. In this chapter, we describe a detailed protocol of production of lentivirus-based SARS-CoV-2 S pseudovirus and its application in study of virus entry and determination of neutralizing antibody titer of human sera against SARS-CoV-2.
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30
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Bergner T, Zech F, Hirschenberger M, Stenger S, Sparrer KMJ, Kirchhoff F, Read C. Near-Native Visualization of SARS-CoV-2 Induced Membrane Remodeling and Virion Morphogenesis. Viruses 2022; 14:v14122786. [PMID: 36560790 PMCID: PMC9784144 DOI: 10.3390/v14122786] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/02/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, leads to profound remodeling of cellular membranes, promoting viral replication and virion assembly. A full understanding of this drastic remodeling and the process of virion morphogenesis remains lacking. In this study, we applied room temperature transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) tomography to visualize the SARS-CoV-2 replication factory in Vero cells, and present our results in comparison with published cryo-EM studies. We obtained cryo-EM-like clarity of the ultrastructure by employing high-pressure freezing, freeze substitution (HPF-FS) and embedding, allowing room temperature visualization of double-membrane vesicles (DMVs) in a near-native state. In addition, our data illustrate the consecutive stages of virion morphogenesis and reveal that SARS-CoV-2 ribonucleoprotein assembly and membrane curvature occur simultaneously. Finally, we show the tethering of virions to the plasma membrane in 3D, and that accumulations of virus particles lacking spike protein in large vesicles are most likely not a result of defective virion assembly at their membrane. In conclusion, this study puts forward a room-temperature EM technique providing near-native ultrastructural information about SARS-CoV-2 replication, adding to our understanding of the interaction of this pandemic virus with its host cell.
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Affiliation(s)
- Tim Bergner
- Central Facility for Electron Microscopy, Ulm University, 89081 Ulm, Germany
| | - Fabian Zech
- Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany
| | | | - Steffen Stenger
- Institute for Microbiology and Hygiene, Ulm University Medical Center, 89081 Ulm, Germany
| | | | - Frank Kirchhoff
- Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany
| | - Clarissa Read
- Central Facility for Electron Microscopy, Ulm University, 89081 Ulm, Germany
- Institute of Virology, Ulm University Medical Center, 89081 Ulm, Germany
- Correspondence:
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31
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Khater I, Nassar A. Potential antiviral peptides targeting the SARS-CoV-2 spike protein. BMC Pharmacol Toxicol 2022; 23:91. [PMID: 36461109 PMCID: PMC9716172 DOI: 10.1186/s40360-022-00627-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 11/15/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND The coronavirus disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an international pandemic and created a public health crisis. The binding of the viral Spike glycoprotein to the human cell receptor angiotensin-converting enzyme 2 (ACE2) initiates viral infection. The development of efficient treatments to combat coronavirus disease is considered essential. METHODS An in silico approach was employed to design amino acid peptide inhibitor against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The designed inhibitor (SARS-CoV-2 PEP 49) consists of amino acids with the α1 helix and the β4 - β5 sheets of ACE2. The PEP-FOLD3 web tool was used to create the 3D structures of the peptide amino acids. Analyzing the interaction between ACE2 and the RBD of the Spike protein for three protein data bank entries (6M0J, 7C8D, and 7A95) indicated that the interacting amino acids were contained inside two regions of ACE2: the α1 helical protease domain (PD) and the β4 - β5 sheets. RESULTS Molecular docking analysis of the designed inhibitor demonstrated that SARS-CoV-2 PEP 49 attaches directly to the ACE2 binding site of the Spike protein with a binding affinity greater than the ACE2, implying that the SARS-CoV-2 PEP 49 model may be useful as a potential RBD binding blocker.
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Affiliation(s)
- Ibrahim Khater
- Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Aaya Nassar
- Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt
- Department of Clinical Research and Leadership, School of Medicine and Health Sciences, George Washington University, Washington DC, USA
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32
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Chan SW. Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation. Front Pharmacol 2022; 13:1007527. [PMID: 36438831 PMCID: PMC9691968 DOI: 10.3389/fphar.2022.1007527] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 10/19/2022] [Indexed: 08/30/2023] Open
Abstract
Virus fusion process is evolutionarily conserved and provides a promising pan-viral target. Cell-cell fusion leads to syncytial formation and has implications in pathogenesis, virus spread and immune evasion. Drugs that target these processes can be developed into anti-virals. Here, we have developed sensitive, rapid, adaptable fusion reporter gene assays as models for plasma membrane and alternative fusion pathways as well as syncytial fusion in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have confirmed their specificity using neutralizing antibodies and specific protease inhibitors. The fusion report gene assays are more sensitive and unbiased than morphological fusion assay. The fusion assays can differentiate between transmembrane serine protease 2 (TMPRSS2)-dependency in TMPRSS2(+) cells and trypsin-dependency in angiotensin-converting enzyme 2 (ACE2)(+)TMPRSS2(-) cells. Moreover, we have identified putative novel fusion processes that are triggered by an acidic pH with and without trypsin. Coupled with morphological fusion criteria, we have found that syncytia formation is enhanced by TMPRSS2 or trypsin. By testing against our top drug hits previously shown to inhibit SARS-CoV-2 pseudovirus infection, we have identified several fusion inhibitors including structurally related lopsided kite-shaped molecules. Our results have important implications in the development of universal blockers and synergistic therapeutics and the small molecule inhibitors can provide important tools in elucidating the fusion process.
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Affiliation(s)
- Shiu-Wan Chan
- Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom
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Role of Nanomaterials in COVID-19 Prevention, Diagnostics, Therapeutics, and Vaccine Development. JOURNAL OF NANOTHERANOSTICS 2022. [DOI: 10.3390/jnt3040011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Facing the deadly pandemic caused by the SARS-CoV-2 virus all over the globe, it is crucial to devote efforts to fighting and preventing this infectious virus. Nanomaterials have gained much attention after the approval of lipid nanoparticle-based COVID-19 vaccines by the United States Food and Drug Administration (USFDA). In light of increasing demands for utilizing nanomaterials in the management of COVID-19, this comprehensive review focuses on the role of nanomaterials in the prevention, diagnostics, therapeutics, and vaccine development of COVID-19. First, we highlight the variety of nanomaterials usage in the prevention of COVID-19. We discuss the advantages of nanomaterials as well as their uses in the production of diagnostic tools and treatment methods. Finally, we review the role of nanomaterials in COVID-19 vaccine development. This review offers direction for creating products based on nanomaterials to combat COVID-19.
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The Mechanisms of Zinc Action as a Potent Anti-Viral Agent: The Clinical Therapeutic Implication in COVID-19. Antioxidants (Basel) 2022; 11:antiox11101862. [PMID: 36290585 PMCID: PMC9598180 DOI: 10.3390/antiox11101862] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/14/2022] [Accepted: 09/16/2022] [Indexed: 11/17/2022] Open
Abstract
The pandemic of COVID-19 was caused by a novel coronavirus termed as SARS-CoV2 and is still ongoing with high morbidity and mortality rates in the whole world. The pathogenesis of COVID-19 is highly linked with over-active immune and inflammatory responses, leading to activated cytokine storm, which contribute to ARDS with worsen outcome. Currently, there is no effective therapeutic drug for the treatment of COVID-19. Zinc is known to act as an immune modulator, which plays an important role in immune defense system. Recently, zinc has been widely considered as an anti-inflammatory and anti-oxidant agent. Accumulating numbers of studies have revealed that zinc plays an important role in antiviral immunity in several viral infections. Several early clinical trials clearly indicate that zinc treatment remarkably decreased the severity of the upper respiratory infection of rhinovirus in humans. Currently, zinc has been used for the therapeutic intervention of COVID-19 in many different clinical trials. Several clinical studies reveal that zinc treatment using a combination of HCQ and zinc pronouncedly reduced symptom score and the rates of hospital admission and mortality in COVID-19 patients. These data support that zinc might act as an anti-viral agent in the addition to its anti-inflammatory and anti-oxidant properties for the adjuvant therapeutic intervention of COVID-19.
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Dimiati H, Umara DA, Naufal I. Covid-19-induced pulmonary hypertension in children, and the use of phosphodiesterase-5 inhibitors. F1000Res 2022; 10:792. [PMID: 39228925 PMCID: PMC11369592 DOI: 10.12688/f1000research.53966.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/06/2022] [Indexed: 09/05/2024] Open
Abstract
Respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first occurred in Wuhan, China, in December 2019 and was declared as a pandemic by WHO. The interaction between the 2019 coronavirus disease (COVID-19) and pulmonary hypertension (PH) in children is not widely known. Phosphodiesterase-5 inhibitors (PDEI), one class of drugs used to treat PH, including sildenafil, can suppress angiotensin type I (AT-1) receptor expression. Furthermore, it reduces proinflammatory cytokines and infiltrates the alveolar, inhibits endothelial and smooth muscle transition, mesenchymal cells in the pulmonary artery, and prevents clotting and thrombosis complications. Sildenafil has shown positive effects by diverting the blood flow to the lungs in such a way that ventilation is adequate and can also be anti-inflammatory.
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Affiliation(s)
- Herlina Dimiati
- Department of Pediatric, Universitas Syiah Kuala, Banda Aceh, Aceh, Indonesia, Indonesia
| | - Dimas Arya Umara
- Department of Cardiology, Universitas Syiah Kuala, Banda Aceh, Aceh, Indonesia, Indonesia
| | - Iflan Naufal
- Department of Family Medicine, Universitas Syiah Kuala, Banda aceh, Aceh, Indonesia, Indonesia
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Pandey A, Madan R, Singh S. Immunology to Immunotherapeutics of SARS-CoV-2: Identification of Immunogenic Epitopes for Vaccine Development. Curr Microbiol 2022; 79:306. [PMID: 36064873 PMCID: PMC9444117 DOI: 10.1007/s00284-022-03003-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 08/16/2022] [Indexed: 11/21/2022]
Abstract
The emergence of COVID19 pandemic caused by SARS-CoV-2 virus has created a global public health and socio-economic crisis. Immunoinformatics-based approaches to investigate the potential antigens is the fastest way to move towards a multiepitope-based vaccine development. This review encompasses the underlying mechanisms of pathogenesis, innate and adaptive immune signaling along with evasion pathways of SARS-CoV-2. Furthermore, it compiles the promiscuous peptides from in silico studies which are subjected to prediction of cytokine milieu using web-based servers. Out of the 434 peptides retrieved from all studies, we have identified 33 most promising T cell vaccine candidates. This review presents a list of the most potential epitopes from several proteins of the virus based on their immunogenicity, homology, conservancy and population coverage studies. These epitopes can form a basis of second generation of vaccine development as the first generation vaccines in various stages of trials mostly focus only on Spike protein. We therefore, propose them as most potential candidates which can be taken up immediately for confirmation by experimental studies.
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Affiliation(s)
- Apoorva Pandey
- Indian Council of Medical Research, V. Ramalingaswami Bhawan, Ansari Nagar, P.O. Box No. 4911, New Delhi, 110029 India
| | - Riya Madan
- Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, Sahibzada Ajit Singh Nagar, Punjab 140306 India
| | - Swati Singh
- Department of Zoology, University of Delhi, Delhi, 110007 India
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SARS-CoV-2 infection: Pathogenesis, Immune Responses, Diagnosis. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.3.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
COVID-19 has emerged as the most alarming infection of the present time instigated by the virus SARS-CoV-2. In spite of advanced research technologies, the exact pathophysiology and treatment of the condition still need to be explored. However, SARS-CoV-2 has several structural and functional similarities that resemble SARS-CoV and MERS-CoV which may be beneficial in exploring the possible treatment and diagnostic strategies for SARS-CoV-2. This review discusses the pathogen phenotype, genotype, replication, pathophysiology, elicited immune response and emerging variants of SARS-CoV-2 and their similarities with other similar viruses. SARS-CoV-2 infection is detected by a number of diagnostics techniques, their advantages and limitations are also discussed in detail. The review also focuses on nanotechnology-based easy and fast detection of SARS-CoV-2 infection. Various pathways which might play a vital role during SARS-CoV-2 infection have been elaborately discussed since immune response plays a major role during viral infections.
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Qiao S, Zhang S, Ge J, Wang X. The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition. FEBS Open Bio 2022; 12:1602-1622. [PMID: 35689514 PMCID: PMC9433818 DOI: 10.1002/2211-5463.13454] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 06/03/2022] [Accepted: 06/09/2022] [Indexed: 12/29/2022] Open
Abstract
Highly pathogenic human coronaviruses (CoV) including SARS-CoV, MERS-CoV and SARS-CoV-2 have emerged over the past two decades, resulting in infectious disease outbreaks that have greatly affected public health. The CoV surface spike (S) glycoprotein mediates receptor binding and membrane fusion for cell entry, playing critical roles in CoV infection and evolution. The S glycoprotein is also the major target molecule for prophylactic and therapeutic interventions, including neutralizing antibodies and vaccines. In this review, we summarize key studies that have revealed the structural basis of S-mediated cell entry of SARS-CoV, MERS-CoV and SARS-CoV-2. Additionally, we discuss the evolution of the S glycoprotein to realize cross-species transmission from the viewpoint of structural biology. Lastly, we describe the recent progress in developing antibodies, nanobodies and peptide inhibitors that target the SARS-CoV-2 S glycoprotein for therapeutic purposes.
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Affiliation(s)
- Shuyuan Qiao
- The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life SciencesTsinghua UniversityBeijingChina
| | - Shuyuan Zhang
- The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life SciencesTsinghua UniversityBeijingChina
| | - Jiwan Ge
- The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life SciencesTsinghua UniversityBeijingChina
| | - Xinquan Wang
- The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life SciencesTsinghua UniversityBeijingChina
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39
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Structural and functional analysis of an inter-Spike bivalent neutralizing antibody against SARS-CoV-2 variants. iScience 2022; 25:104431. [PMID: 35607524 PMCID: PMC9116965 DOI: 10.1016/j.isci.2022.104431] [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: 03/14/2022] [Revised: 04/19/2022] [Accepted: 05/13/2022] [Indexed: 12/03/2022] Open
Abstract
The different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted most public concern because they caused “wave and wave” COVID-19 pandemic. The initial step of viral infection is mediated by the SARS-CoV-2 Spike (S) protein, which mediates the receptor recognition and membrane fusion between virus and host cells. Neutralizing antibodies (nAbs) targeting the S protein of SARS-CoV-2 have become promising candidates for clinical intervention strategy, while multiple studies have shown that different variants have enhanced infectivity and antibody resistance. Here, we explore the structure and function of STS165, a broadly inter-Spike bivalent nAb against SARS-CoV-2 variants and even SARS-CoV, contributing to further understanding of the working mechanism of nAbs.
STS165 broadly neutralizes different variants of SARS-CoV-2 and even SARS-CoV STS165 exhibits inter-Spike bivalent binding characteristics STS165 may work as an ideal partner to form therapeutic antibody cocktails
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40
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Wang L, Jiang L, Pan D, Wang Q, Yin Z, Kang Z, Tian H, Geng X, Shao J, Pan W, Yin J, Fang L, Wang Y, Zhang W, Li Z, Zheng J, Hu W, Pan Y, Yu D, Guo S, Lu W, Li Q, Zhou Y, Xu H. Novel approach by natural language processing for COVID-19 knowledge discovery. Biomed J 2022; 45:472-481. [PMID: 35367669 PMCID: PMC8970612 DOI: 10.1016/j.bj.2022.03.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 02/25/2022] [Accepted: 03/21/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The impact of COVID-19 on public health has mandated an 'all hands on deck' scientific response. The current clinical study and basic research on COVID-19 are mainly based on existing publications or our knowledge of coronavirus. However, efficiently retrieval of accurate, relevant knowledge on COVID-19 can pose significant challenges for researchers. METHODS To improve quality in accessing important literature findings, we developed a novel natural language processing (NLP) method to automatically recognize the associations among potential targeted host organ systems, associated clinical manifestations, and pathways. We further validated these associations through clinician experts' evaluations and prioritize candidate drug targets through bioinformatics network analysis. RESULTS We found that the angiotensin-converting enzyme 2 (ACE2), a receptor that SARS-CoV-2 required for cell entry, is associated with cardiovascular and endocrine organ system and diseases. Furthermore, we found SARS-CoV-2 is associated with some important pathways such as IL-6, TNF-alpha, and IL-1 beta-induced dyslipidemia, which are related to inflammation, lipogenesis, and oxidative stress mechanisms, suggesting potential drug candidates. CONCLUSION We prioritized the list of therapeutic targets involved in antiviral and immune modulating drugs for experimental validation, rendering it valuable during public health crises marked by stresses on clinical and research capacity. Our automatic intelligence pipeline also contributes to other novel and emerging disease management and treatments in the future.
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Affiliation(s)
- Li Wang
- Medical School, Nantong University, Nantong, China; Research Center for Intelligence Information Technology, Nantong University, Nantong, China
| | - Lei Jiang
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Dongyan Pan
- Department of Ophthalmology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Qinghua Wang
- Medical School, Nantong University, Nantong, China
| | - Zeyu Yin
- Medical School, Nantong University, Nantong, China
| | - Zijian Kang
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Haoran Tian
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xuqiang Geng
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jinsong Shao
- Public Health School, Nantong University, Nantong, China
| | - Wenjie Pan
- Medical School, Nantong University, Nantong, China
| | - Jian Yin
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Li Fang
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, PA, USA
| | - Yue Wang
- Department of Histology & Embryology, Second Military Medical University, Shanghai, China
| | - Weide Zhang
- Big Data and Artificial Intelligence Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhixiu Li
- Translational Genomics Group, Institute of Health and Biomedical Innovation, Queensland University of Technology at Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia
| | - Jun Zheng
- School of Data Science & Engineering, East China Normal University, Shanghai, China
| | - Wenxin Hu
- School of Data Science & Engineering, East China Normal University, Shanghai, China
| | - Yunbao Pan
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Dong Yu
- Center for Translational Medicine, Second Military Medical University, Shanghai, China
| | - Shicheng Guo
- Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, USA
| | - Wei Lu
- NO.905 Hospital, Shanghai, China
| | - Qiang Li
- Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Yunyun Zhou
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, PA, USA
| | - Huji Xu
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China; Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China; School of Clinical Medicine, Tsinghua University, Beijing, China.
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41
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Francesconi O, Donnici L, Fragai M, Pesce E, Bombaci M, Fasciani A, Manganaro L, Conti M, Grifantini R, De Francesco R, Nativi C, Roelens S. Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2. iScience 2022; 25:104239. [PMID: 35434540 PMCID: PMC8996466 DOI: 10.1016/j.isci.2022.104239] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 03/21/2022] [Accepted: 04/06/2022] [Indexed: 11/26/2022] Open
Abstract
Developing strategies against the SARS-CoV-2 is currently a main research subject. SARS-CoV-2 infects host cells by binding to human ACE2 receptors. Both, virus and ACE2, are highly glycosylated, and exploiting glycans of the SARS-CoV-2 envelope as binding sites for ACE2 represents a virus strategy for attacking the human host. We report here that a family of mannose-binding synthetic carbohydrate-binding agents (CBAs) inhibits SARS-CoV-2 infection, showing broad neutralizing activity vs. several variants of the spike protein. Preliminary tests indicated that the investigated CBAs interact with the spike protein rather than with ACE2. For a lead compound (IDS060), which has been selected among others for its lack of cytotoxicity, evidence of binding to the RBD of the spike protein has been found by NMR experiments, while competitive binding assays in the presence of IDS060 showed inhibition of binding of RBD to hACE2, although neutralizing activity was also observed with variants showing reduced or depleted binding.
Mannose-binding CBAs inhibit SARS-CoV-2 infection showing broad neutralizing activity CBAs interact with the spike protein rather than with ACE2 receptors The non-toxic CBA IDS060 binds to the spike RBD and inhibits binding of RBD to hACE2
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Affiliation(s)
- Oscar Francesconi
- Dipartimento di Chimica, DICUS, University of Florence, Florence, Italy
| | - Lorena Donnici
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Marco Fragai
- Dipartimento di Chimica, DICUS, University of Florence, Florence, Italy.,CERM, University of Florence, Florence, Italy
| | - Elisa Pesce
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Mauro Bombaci
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Alessandra Fasciani
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Lara Manganaro
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.,Dipartimento di Scienze Farmacologiche e Biomolecolari, University of Milan, Milan, Italy
| | - Matteo Conti
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Renata Grifantini
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Raffaele De Francesco
- Fondazione INGM - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.,Dipartimento di Scienze Farmacologiche e Biomolecolari, University of Milan, Milan, Italy
| | - Cristina Nativi
- Dipartimento di Chimica, DICUS, University of Florence, Florence, Italy
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Hernández-Ochoa B, Ortega-Cuellar D, González-Valdez A, Cárdenas-Rodríguez N, Mendoza-Torreblanca JG, Contreras-García IJ, Pichardo-Macías LA, Bandala C, Gómez-Manzo S. COVID-19 in G6PD-deficient patients, oxidative stress, and neuropathology. Curr Top Med Chem 2022; 22:1307-1325. [PMID: 35578850 DOI: 10.2174/1568026622666220516111122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 03/01/2022] [Accepted: 03/12/2022] [Indexed: 11/22/2022]
Abstract
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that regulates energy metabolism mainly through the pentose phosphate pathway (PPP). It is well known that this enzyme participates in the antioxidant/oxidant balance via the synthesis of energy-rich molecules: nicotinamide adenine dinucleotide phosphate reduced (NADPH), the reduced form of flavin adenine dinucleotide (FADH) and glutathione (GSH), controlling reactive oxygen species generation. Coronavirus disease 19 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered a public health problem which has caused approximately 4.5 million deaths since December 2019. In relation to the role of G6PD in COVID-19 development, it is known from the existing literature that G6PD-deficient patients infected with SARS-CoV-2 are more susceptible to thrombosis and hemolysis, suggesting that G6PD deficiency facilitates infection by SARS-CoV-2. In relation to G6PD and neuropathology, it has been observed that deficiency of this enzyme is also present with an increase in oxidative markers. In relation to the role of G6PD and the neurological manifestations of COVID-19, it has been reported that the enzymatic deficiency in patients infected with SARS-CoV-2 exacerbates the disease, and, in some clinical reports, an increase in hemolysis and thrombosis was observed when patients were treated with hydroxychloroquine (OH-CQ), a drug with oxidative properties. In the present work, we summarize the evidence of the role of G6PD in COVID-19 and its possible role in the generation of oxidative stress and glucose metabolism deficits and inflammation present in this respiratory disease and its progression including neurological manifestations.
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Affiliation(s)
- Beatriz Hernández-Ochoa
- Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City, 06720, Mexico
| | - Daniel Ortega-Cuellar
- Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
| | - Abigail González-Valdez
- Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
| | - Noemí Cárdenas-Rodríguez
- Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
| | | | | | - Luz Adriana Pichardo-Macías
- Departamento de Fisiología, Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Mexico City, 07738, Mexico
| | - Cindy Bandala
- Division de Neurociencias, Instituto Nacional de Rehabilitación, Secretaría de Salud, Mexico City, 14389, Mexico.,Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, 11340, Mexico
| | - Saúl Gómez-Manzo
- Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
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Biswas S, Mahmud S, Mita MA, Afrose S, Hasan MR, Paul GK, Shimu MSS, Uddin MS, Zaman S, Park MN, Siyadatpanah A, Obaidullah AJ, Saleh MA, Simal-Gandara J, Kim B. The Emergence of SARS-CoV-2 Variants With a Lower Antibody Response: A Genomic and Clinical Perspective. Front Med (Lausanne) 2022; 9:825245. [PMID: 35602477 PMCID: PMC9121733 DOI: 10.3389/fmed.2022.825245] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 03/21/2022] [Indexed: 12/19/2022] Open
Abstract
The emergence of several novel SARS-CoV-2 variants regarded as variants of concern (VOCs) has exacerbated pathogenic and immunologic prominences, as well as reduced diagnostic sensitivity due to phenotype modification-capable mutations. Furthermore, latent and more virulent strains that have arisen as a result of unique mutations with increased evolutionary potential represent a threat to vaccine effectiveness in terms of incoming and existing variants. As a result, resisting natural immunity, which leads to higher reinfection rates, and avoiding vaccination-induced immunization, which leads to a lack of vaccine effectiveness, has become a crucial problem for public health around the world. This study attempts to review the genomic variation and pandemic impact of emerging variations of concern based on clinical characteristics management and immunization effectiveness. The goal of this study is to gain a better understanding of the link between genome level polymorphism, clinical symptom manifestation, and current vaccination in the instance of VOCs.
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Affiliation(s)
- Suvro Biswas
- Miocrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Shafi Mahmud
- Miocrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Mohasana Akter Mita
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Shamima Afrose
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Md. Robiul Hasan
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Gobindo Kumar Paul
- Miocrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | | | - Md. Salah Uddin
- Miocrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Shahriar Zaman
- Miocrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Abolghasem Siyadatpanah
- Ferdows School of Paramedical and Health, Birjand University of Medical Sciences, Birjand, Iran
| | - Ahmad J. Obaidullah
- Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Md. Abu Saleh
- Miocrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, University of Vigo, Ourense, Spain
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
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Unique Mode of Antiviral Action of a Marine Alkaloid against Ebola Virus and SARS-CoV-2. Viruses 2022; 14:v14040816. [PMID: 35458549 PMCID: PMC9028129 DOI: 10.3390/v14040816] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/24/2022] [Accepted: 04/02/2022] [Indexed: 11/16/2022] Open
Abstract
Lamellarin α 20-sulfate is a cell-impenetrable marine alkaloid that can suppress infection that is mediated by the envelope glycoprotein of human immunodeficiency virus type 1. We explored the antiviral action and mechanisms of this alkaloid against emerging enveloped RNA viruses that use endocytosis for infection. The alkaloid inhibited the infection of retroviral vectors that had been pseudotyped with the envelope glycoprotein of Ebola virus and SARS-CoV-2. The antiviral effects of lamellarin were independent of the retrovirus Gag-Pol proteins. Interestingly, although heparin and dextran sulfate suppressed the cell attachment of vector particles, lamellarin did not. In silico structural analyses of the trimeric glycoprotein of the Ebola virus disclosed that the principal lamellarin-binding site is confined to a previously unappreciated cavity near the NPC1-binding site and fusion loop, whereas those for heparin and dextran sulfate were dispersed across the attachment and fusion subunits of the glycoproteins. Notably, lamellarin binding to this cavity was augmented under conditions where the pH was 5.0. These results suggest that the final action of the alkaloid against Ebola virus is specific to events following endocytosis, possibly during conformational glycoprotein changes in the acidic environment of endosomes. Our findings highlight the unique biological and physicochemical features of lamellarin α 20-sulfate and should lead to the further use of broadly reactive antivirals to explore the structural mechanisms of virus replication.
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Yan Q, Liu X, Sun Y, Zeng W, Li Y, Zhao F, Wu K, Fan S, Zhao M, Chen J, Yi L. Swine Enteric Coronavirus: Diverse Pathogen–Host Interactions. Int J Mol Sci 2022; 23:ijms23073953. [PMID: 35409315 PMCID: PMC8999375 DOI: 10.3390/ijms23073953] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 12/23/2022] Open
Abstract
Swine enteric coronavirus (SeCoV) causes acute gastroenteritis and high mortality in newborn piglets. Since the last century, porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) have swept farms all over the world and caused substantial economic losses. In recent years, porcine delta coronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) have been emerging SeCoVs. Some of them even spread across species, which made the epidemic situation of SeCoV more complex and changeable. Recent studies have begun to reveal the complex SeCoV–host interaction mechanism in detail. This review summarizes the current advances in autophagy, apoptosis, and innate immunity induced by SeCoV infection. These complex interactions may be directly involved in viral replication or the alteration of some signal pathways.
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Affiliation(s)
- Quanhui Yan
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Xiaodi Liu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Yawei Sun
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Weijun Zeng
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Yuwan Li
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Feifan Zhao
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Keke Wu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Shuangqi Fan
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Mingqiu Zhao
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Jinding Chen
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
- Correspondence: (J.C.); (L.Y.); Tel.: +86-20-8528-8017 (J.C. & L.Y.)
| | - Lin Yi
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; (Q.Y.); (X.L.); (Y.S.); (W.Z.); (Y.L.); (F.Z.); (K.W.); (S.F.); (M.Z.)
- Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
- Correspondence: (J.C.); (L.Y.); Tel.: +86-20-8528-8017 (J.C. & L.Y.)
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Yépez Y, Marcano-Ruiz M, Bezerra RS, Fam B, Ximenez JPB, Silva WA, Bortolini MC. Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm. Genet Mol Biol 2022; 45:e20210309. [PMID: 35266951 PMCID: PMC8908351 DOI: 10.1590/1678-4685-gmb-2021-0309] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/29/2021] [Indexed: 12/11/2022] Open
Abstract
Our goal was to describe in more detail the evolutionary history of Gamma and two derived lineages (P.1.1 and P.1.2), which are part of the arms race that SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive selection in 12 genes/ORFs: Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6, ORF7a, ORF7b, ORF8, and ORF10. Some diagnostic sites for Gamma lacked a signature of positive selection in our study, but these were not fixed, apparently escaping the action of purifying selection. Our network analyses revealed branches leading to expanding haplotypes with sites under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2 exclusive haplotype H_5 originated from a non-synonymous mutational step (H3509Y) in H_1 of ORF1a. The selected allele, 3509Y, represents an adaptive novelty involving ORF1a of P.1. Finally, we discuss how phenomena such as epistasis and antagonistic pleiotropy could limit the emergence of new alleles (and combinations thereof) in SARS-COV-2 lineages, maintaining infectivity in humans, while providing rapid response capabilities to face the arms race triggered by host immuneresponses.
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Affiliation(s)
- Yuri Yépez
- Universidade Federal do Rio Grande do Sul, Departamento de Genética,
Laboratório de Evolução Humana e Molecular, Porto Alegre, RS, Brazil
| | - Mariana Marcano-Ruiz
- Universidade Federal do Rio Grande do Sul, Departamento de Genética,
Laboratório de Evolução Humana e Molecular, Porto Alegre, RS, Brazil
| | - Rafael S Bezerra
- Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto,
Departamento de Genética, Ribeirão Preto, SP, Brazil
| | - Bibiana Fam
- Universidade Federal do Rio Grande do Sul, Departamento de Genética,
Laboratório de Evolução Humana e Molecular, Porto Alegre, RS, Brazil
| | - João PB Ximenez
- Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto,
Departamento de Genética, Ribeirão Preto, SP, Brazil
| | - Wilson A Silva
- Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto,
Departamento de Genética, Ribeirão Preto, SP, Brazil
- Instituto de Pesquisa do Câncer de Guarapuava, Guarapuava, PR,
Brazil
| | - Maria Cátira Bortolini
- Universidade Federal do Rio Grande do Sul, Departamento de Genética,
Laboratório de Evolução Humana e Molecular, Porto Alegre, RS, Brazil
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Duan Y, Yuan C, Suo X, Cao L, Kong X, Li X, Zheng H, Wang Q. TET2 is Required for Type I IFN-mediated Inhibition of Bat-Origin Swine Acute Diarrhea Syndrome Coronavirus. J Med Virol 2022; 94:3251-3256. [PMID: 35211991 DOI: 10.1002/jmv.27673] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/16/2022] [Accepted: 02/20/2022] [Indexed: 11/07/2022]
Abstract
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered bat-origin coronavirus with fatal pathogenicity for neonatal piglets. There is no vaccine to prevent SADS-CoV infection or clinically approved drugs targeting SADS-CoV. Therefore, unraveling cellular factors that regulate SADS-CoV for cell entry is critical to understanding the viral transmission mechanism and provides a potential therapeutic target for SADS-CoV cure. Here, we showed that type I interferon (IFN-I) pretreatment potently blocks SADS-CoV entry into cells using lentiviral pseudo-virions as targets whose entry is driven by the SADS-CoV Spike glycoprotein. IFN-I-mediated inhibition of SADS-CoV entry and replication was dramatically impaired in the absence of TET2. These results suggest TET2 is found to serve as a checkpoint of IFN-I-meditated inhibition on the cell entry of SADS-CoV, and our discovery might constitute a novel treatment option to combat against SADS-CoV. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Yueyue Duan
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu, 600103, China.,State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.,Chengdu National Agricultural Science and Technology Center, Chengdu, 600103, China
| | - Cong Yuan
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu, 600103, China.,State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.,Chengdu National Agricultural Science and Technology Center, Chengdu, 600103, China
| | - Xuepeng Suo
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu, 600103, China.,State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.,Chengdu National Agricultural Science and Technology Center, Chengdu, 600103, China
| | - Liyan Cao
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu, 600103, China.,State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.,Chengdu National Agricultural Science and Technology Center, Chengdu, 600103, China
| | - Xiangyu Kong
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu, 600103, China.,State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.,Chengdu National Agricultural Science and Technology Center, Chengdu, 600103, China
| | - Xiangtong Li
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu, 600103, China.,State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.,Chengdu National Agricultural Science and Technology Center, Chengdu, 600103, China
| | - Haixue Zheng
- State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Qi Wang
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu, 600103, China.,State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.,Chengdu National Agricultural Science and Technology Center, Chengdu, 600103, China
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48
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Known Cellular and Receptor Interactions of Animal and Human Coronaviruses: A Review. Viruses 2022; 14:v14020351. [PMID: 35215937 PMCID: PMC8878323 DOI: 10.3390/v14020351] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/03/2022] [Accepted: 02/05/2022] [Indexed: 12/12/2022] Open
Abstract
This article aims to review all currently known interactions between animal and human coronaviruses and their cellular receptors. Over the past 20 years, three novel coronaviruses have emerged that have caused severe disease in humans, including SARS-CoV-2 (severe acute respiratory syndrome virus 2); therefore, a deeper understanding of coronavirus host-cell interactions is essential. Receptor-binding is the first stage in coronavirus entry prior to replication and can be altered by minor changes within the spike protein-the coronavirus surface glycoprotein responsible for the recognition of cell-surface receptors. The recognition of receptors by coronaviruses is also a major determinant in infection, tropism, and pathogenesis and acts as a key target for host-immune surveillance and other potential intervention strategies. We aim to highlight the need for a continued in-depth understanding of this subject area following on from the SARS-CoV-2 pandemic, with the possibility for more zoonotic transmission events. We also acknowledge the need for more targeted research towards glycan-coronavirus interactions as zoonotic spillover events from animals to humans, following an alteration in glycan-binding capability, have been well-documented for other viruses such as Influenza A.
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49
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Gusev E, Sarapultsev A, Solomatina L, Chereshnev V. SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19. Int J Mol Sci 2022; 23:1716. [PMID: 35163638 PMCID: PMC8835786 DOI: 10.3390/ijms23031716] [Citation(s) in RCA: 154] [Impact Index Per Article: 51.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/31/2022] [Accepted: 02/01/2022] [Indexed: 12/13/2022] Open
Abstract
The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus's protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2's ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.
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Affiliation(s)
- Evgenii Gusev
- Laboratory of Immunology of Inflammation, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia
| | - Alexey Sarapultsev
- Laboratory of Immunology of Inflammation, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 454080 Chelyabinsk, Russia
| | - Liliya Solomatina
- Laboratory of Immunology of Inflammation, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia
| | - Valeriy Chereshnev
- Laboratory of Immunology of Inflammation, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia
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50
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Khan MA, Bin Islam S, Rakib MU, Alam D, Hossen MM, Tania M, Asad A. Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Validation
and Current Progress in Trials. CORONAVIRUSES 2022; 3. [DOI: 10.2174/2666796701999201204122819] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 11/16/2020] [Accepted: 11/11/2020] [Indexed: 07/28/2024]
Abstract
Background:
Currently, the present world is facing a new deadly challenge against a pandemic disease called
COVID-19, which is caused by a coronavirus, named SARS-CoV-2. To date, there is no drug or vaccine that can treat
COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This
review article discussed and compared those drugs which are running ahead in COVID-19 treatments.
Methods:
We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press release of WHO, NIH and FDA for
articles about COVID-19, and reviewed them.
Results:
Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin,
corticosteroids and interferons have been found effective in some extents, and partially approved by FDA and WHO to treat
COVID-19 at different phases of pandemic. However, some of these drugs have been disapproved later, although clinical
trials are going on. In parallel, plasma therapy has been found fruitful in some extents too, and a number of vaccine trails are
going on.
Conclusions:
This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how
drugs could act on this virus with the comparative discussion on progress and backwards of major drugs used till date,
which might be beneficial for choosing therapies against COVID-19 in different countries.
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Affiliation(s)
- Md. Asaduzzaman Khan
- The Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical
University, Luzhou, Sichuan 646000, China
| | - Shad Bin Islam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Mejbah Uddin Rakib
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Didarul Alam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Md. Munnaf Hossen
- Department of Immunology, Health Science Center, Shenzhen,
University, Shenzhen, Guangdong 518060, China
| | - Mousumi Tania
- Division of Molecular Cancer, Red Green Research Center,
Dhaka, Bangladesh
| | - Asaduzzaman Asad
- Department of Biochemistry and Molecular Biology, Jahangirnagar University; and International
Center for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
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