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Khazir J, Ahmed S, Thakur RK, Hussain M, Gandhi SG, Babbar S, Mir SA, Shafi N, Tonfack LB, Rajpal VR, Maqbool T, Mir BA, Peer LA. Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19. Curr Top Med Chem 2024; 24:614-633. [PMID: 38477206 DOI: 10.2174/0115680266276749240206101847] [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: 09/28/2023] [Revised: 12/30/2023] [Accepted: 01/10/2024] [Indexed: 03/14/2024]
Abstract
COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19.
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Affiliation(s)
- Jabeena Khazir
- Department of Chemistry, HKM Govt. Degree College Eidgah, Cluster University Srinagar, J&K, 190001, India
| | - Sajad Ahmed
- Indian Institute of Integrative Medicine, Canal Road Jammu, 180001, J&K, India
| | - Rakesh Kr Thakur
- Amity Institute of Biotechnology, Amity University, Noida, 201313, India
| | - Manzoor Hussain
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, Punjab, India
- Department of Botany, North Campus, University of Kashmir, Delina, Baramulla, J&K, 193103, India
| | - Sumit G Gandhi
- Indian Institute of Integrative Medicine, Canal Road Jammu, 180001, J&K, India
| | - Sadhana Babbar
- Department of Botany, Swami Shradhanand College, University of Delhi, Delhi, 110036, India
| | - Shabir Ahmad Mir
- Department of Medical Laboratory Sciences, College of Applied Medical Science, Majmaah University, Al Majmaah, 11952, Saudi Arabia
| | - Nusrat Shafi
- Department of Chemistry, HKM Govt. Degree College Eidgah, Cluster University Srinagar, J&K, 190001, India
| | - Libert Brice Tonfack
- Laboratory of Biotechnology and Environment, Department of Plant Biology, Faculty of Science, University of Yaounde I, PO Box 812, Yaounde, Cameroon
| | - Vijay Rani Rajpal
- Department of Botany, Hans Raj College, University of Delhi, Delhi, 110007, India
| | - Tariq Maqbool
- Laboratory of Nanotherapeutics and Regenerative Medicine, University of Kashmir, Srinagar, 190006, India
| | - Bilal Ahmad Mir
- Department of Botany, North Campus, University of Kashmir, Delina, Baramulla, J&K, 193103, India
| | - Latif Ahmad Peer
- Department of Botany, University of Kashmir, Srinagar, J&K, 190006, India
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Takamiya D, Takahashi H, Nakamura A, Xia Y, Kuda T. Effect of Lactiplantibacillus plantarum fermentation on the in-vitro antioxidant and angiotensin I-converting enzyme-inhibitory properties of turmeric, coriander, cumin, and red chili pepper suspensions. BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 2023. [DOI: 10.1016/j.bcab.2023.102610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Jamal QMS. Antiviral Potential of Plants against COVID-19 during Outbreaks-An Update. Int J Mol Sci 2022; 23:13564. [PMID: 36362351 PMCID: PMC9655040 DOI: 10.3390/ijms232113564] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 10/06/2022] [Accepted: 11/02/2022] [Indexed: 12/01/2023] Open
Abstract
Several human diseases are caused by viruses, including cancer, Type I diabetes, Alzheimer's disease, and hepatocellular carcinoma. In the past, people have suffered greatly from viral diseases such as polio, mumps, measles, dengue fever, SARS, MERS, AIDS, chikungunya fever, encephalitis, and influenza. Recently, COVID-19 has become a pandemic in most parts of the world. Although vaccines are available to fight the infection, their safety and clinical trial data are still questionable. Social distancing, isolation, the use of sanitizer, and personal productive strategies have been implemented to prevent the spread of the virus. Moreover, the search for a potential therapeutic molecule is ongoing. Based on experiences with outbreaks of SARS and MERS, many research studies reveal the potential of medicinal herbs/plants or chemical compounds extracted from them to counteract the effects of these viral diseases. COVID-19's current status includes a decrease in infection rates as a result of large-scale vaccination program implementation by several countries. But it is still very close and needs to boost people's natural immunity in a cost-effective way through phytomedicines because many underdeveloped countries do not have their own vaccination facilities. In this article, phytomedicines as plant parts or plant-derived metabolites that can affect the entry of a virus or its infectiousness inside hosts are described. Finally, it is concluded that the therapeutic potential of medicinal plants must be analyzed and evaluated entirely in the control of COVID-19 in cases of uncontrollable SARS infection.
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Affiliation(s)
- Qazi Mohammad Sajid Jamal
- Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah 52741, Saudi Arabia
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Zhao Y, Deng S, Bai Y, Guo J, Kai G, Huang X, Jia X. Promising natural products against SARS-CoV-2: Structure, function, and clinical trials. Phytother Res 2022; 36:3833-3858. [PMID: 35932157 PMCID: PMC9538226 DOI: 10.1002/ptr.7580] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 07/04/2022] [Accepted: 07/07/2022] [Indexed: 01/18/2023]
Abstract
The corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-COV-2) poses a severe threat to human health and still spreads globally. Due to the high mutation ratio and breakthrough infection rate of the virus, vaccines and anti-COVID-19 drugs require continual improvements. Drug screening research has shown that some natural active products can target the critical proteins of SARS-CoV-2, including 3CLpro, ACE2, FURIN, and RdRp, which could produce great inhibitory effects on SARS-COV-2. In addition, some natural products have displayed activities of immunomodulation, antiinflammatory, and antihepatic failure in COVID-19 clinical trials, which may relate to their non-monomeric structures. However, further evaluation and high-quality assessments, including safety verification tests, drug interaction tests, and clinical trials, are needed to substantiate natural products' multi-target and multi-pathway effects on COVID-19. Here, we review the literature on several promising active natural products that may act as vaccine immune enhancers or provide targeted anti-COVID-19 drugs. The structures, mechanisms of action, and research progress of these natural products are analyzed, to hopefully provide effective ideas for the development of targeted drugs that possess better structure, potency, and safety.
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Affiliation(s)
- Yan Zhao
- Life Science and EngineeringSouthwest Jiaotong UniversityChengduChina
| | - Shanshan Deng
- Sichuan Key Laboratory of Noncoding RNA and DrugsChengdu Medical CollegeChengduChina
| | - Yujiao Bai
- Sichuan Key Laboratory of Noncoding RNA and DrugsChengdu Medical CollegeChengduChina
| | - Jinlin Guo
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest ChinaChengdu University of Traditional Chinese MedicineChengduChina
| | - Guoyin Kai
- Zhejiang Chinese Medical UniversityHangzhouChina
| | - Xinhe Huang
- Life Science and EngineeringSouthwest Jiaotong UniversityChengduChina
| | - Xu Jia
- Sichuan Key Laboratory of Noncoding RNA and DrugsChengdu Medical CollegeChengduChina
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Bošković M, Živković M, Koricanac G, Tepavcevic S, Zec M, Debeljak-Martacic J, Stanković A. Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart. Front Physiol 2022; 13:942459. [PMID: 36213224 PMCID: PMC9533082 DOI: 10.3389/fphys.2022.942459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 09/06/2022] [Indexed: 11/13/2022] Open
Abstract
Increased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health.
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Affiliation(s)
- Maja Bošković
- Laboratory for Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Maja Živković
- Laboratory for Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Goran Koricanac
- Laboratory for Molecular Biology and Endocrinology, “VINČA” Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Snezana Tepavcevic
- Laboratory for Molecular Biology and Endocrinology, “VINČA” Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Manja Zec
- School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States
| | - Jasmina Debeljak-Martacic
- Centre of Excellence in Nutrition and Metabolism Research, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Stanković
- Laboratory for Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
- *Correspondence: Aleksandra Stanković,
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Nepali K, Sharma R, Sharma S, Thakur A, Liou JP. Beyond the vaccines: a glance at the small molecule and peptide-based anti-COVID19 arsenal. J Biomed Sci 2022; 29:65. [PMID: 36064696 PMCID: PMC9444709 DOI: 10.1186/s12929-022-00847-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/16/2022] [Indexed: 02/08/2023] Open
Abstract
Unprecedented efforts of the researchers have been witnessed in the recent past towards the development of vaccine platforms for the control of the COVID-19 pandemic. Albeit, vaccination stands as a practical strategy to prevent SARS-CoV-2 infection, supplementing the anti-COVID19 arsenal with therapeutic options such as small molecules/peptides and antibodies is being conceived as a prudent strategy to tackle the emerging SARS-CoV-2 variants. Noteworthy to mention that collective efforts from numerous teams have led to the generation of a voluminous library composed of chemically and mechanistically diverse small molecules as anti-COVID19 scaffolds. This review article presents an overview of medicinal chemistry campaigns and drug repurposing programs that culminated in the identification of a plethora of small molecule-based anti-COVID19 drugs mediating their antiviral effects through inhibition of proteases, S protein, RdRp, ACE2, TMPRSS2, cathepsin and other targets. In light of the evidence ascertaining the potential of small molecule drugs to approach conserved proteins required for the viral replication of all coronaviruses, accelerated FDA approvals are anticipated for small molecules for the treatment of COVID19 shortly. Though the recent attempts invested in this direction in pursuit of enrichment of the anti-COVID-19 armoury (chemical tools) are praiseworthy, some strategies need to be implemented to extract conclusive benefits of the recently reported small molecule viz. (i) detailed preclinical investigation of the generated anti-COVID19 scaffolds (ii) in-vitro profiling of the inhibitors against the emerging SARS-CoV-2 variants (iii) development of assays enabling rapid screening of the libraries of anti-COVID19 scaffold (iv) leveraging the applications of machine learning based predictive models to expedite the anti-COVID19 drug discovery campaign (v) design of antibody-drug conjugates.
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Affiliation(s)
- Kunal Nepali
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan
- TMU Research Center for Drug Discovery, Taipei Medical University, Taipei, 11031, Taiwan
| | - Ram Sharma
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan
| | - Sachin Sharma
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan
| | - Amandeep Thakur
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan
| | - Jing-Ping Liou
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
- TMU Research Center for Drug Discovery, Taipei Medical University, Taipei, 11031, Taiwan.
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Structural insights revealed by crystal structure of B38-CAP, an isoenzyme of carboxypeptidase ACE2, the receptor of SARS-CoV-2. Biochem Biophys Res Commun 2022; 606:17-22. [PMID: 35338854 PMCID: PMC8930179 DOI: 10.1016/j.bbrc.2022.03.077] [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: 03/06/2022] [Accepted: 03/15/2022] [Indexed: 11/20/2022]
Abstract
The worldwide pandemic of Coronavirus disease 2019 (COVID-19) is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and further worsened by the emergence of a variety of SARS-CoV-2 variants. Angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase of M32 family, serves as the receptor of SARS-CoV-2 and key regulator of host renin-angiotensin system (RAS), both of which are mainly mediated via the carboxypeptidase domain of ACE2 (sACE2) or its activity. sACE2 is thus promising in the treatment of COVID-19 but unfortunately weakened by its unstrigent substrate preference and complex interplay with host RAS. B38-CAP, an isoenzyme of ACE2, partically compensates these defects but still encounters the problem related to carboxypeptidase activity and specificity. In this study, we firstly determined the crystal structure of B38-CAP at a resolution of 2.44 Å which exists in dimeric form with the non-crystallographic two-fold axis being in coincidence with the crystallographic two-fold axis. Further structural analysis revealed the structural conservatism feature among M32 family, particularly the catalytic core and moreover lead us to hypothesize that conformational flexibility might play an pivotal role in the catalysis of B38-CAP and ACE2. The work provided here presents key features of the M32 family carboxypeptidase and provides structural basis for further development of B38-CAP-based anti-SARS-CoV-2 drugs.
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Xiang R, Yu Z, Wang Y, Wang L, Huo S, Li Y, Liang R, Hao Q, Ying T, Gao Y, Yu F, Jiang S. Recent advances in developing small-molecule inhibitors against SARS-CoV-2. Acta Pharm Sin B 2022; 12:1591-1623. [PMID: 34249607 PMCID: PMC8260826 DOI: 10.1016/j.apsb.2021.06.016] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 06/13/2021] [Accepted: 06/23/2021] [Indexed: 02/07/2023] Open
Abstract
The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.
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Affiliation(s)
- Rong Xiang
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Zhengsen Yu
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Yang Wang
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Lili Wang
- Research Center of Chinese Jujube, Hebei Agricultural University, Baoding 071001, China
| | - Shanshan Huo
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Yanbai Li
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Ruiying Liang
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Qinghong Hao
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Tianlei Ying
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 200032, China
| | - Yaning Gao
- Beijing Pharma and Biotech Center, Beijing 100176, China,Corresponding authors. Tel.: +86 21 54237673, fax: +86 21 54237465 (Shibo Jiang); Tel.: +86 312 7528935, fax: +86 312 7521283 (Fei Yu); Tel.: +86 10 62896868; fax: +86 10 62899978, (Yanning Gao).
| | - Fei Yu
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China,Corresponding authors. Tel.: +86 21 54237673, fax: +86 21 54237465 (Shibo Jiang); Tel.: +86 312 7528935, fax: +86 312 7521283 (Fei Yu); Tel.: +86 10 62896868; fax: +86 10 62899978, (Yanning Gao).
| | - Shibo Jiang
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 200032, China,Corresponding authors. Tel.: +86 21 54237673, fax: +86 21 54237465 (Shibo Jiang); Tel.: +86 312 7528935, fax: +86 312 7521283 (Fei Yu); Tel.: +86 10 62896868; fax: +86 10 62899978, (Yanning Gao).
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Bardelčíková A, Miroššay A, Šoltýs J, Mojžiš J. Therapeutic and prophylactic effect of flavonoids in post-COVID-19 therapy. Phytother Res 2022; 36:2042-2060. [PMID: 35302260 PMCID: PMC9111001 DOI: 10.1002/ptr.7436] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/16/2022] [Accepted: 02/21/2022] [Indexed: 12/17/2022]
Abstract
The high incidence of post-covid symptoms in humans confirms the need for effective treatment. Due to long-term complications across several disciplines, special treatment programs emerge for affected patients, emphasizing multidisciplinary care. For these reasons, we decided to look at current knowledge about possible long-term complications of COVID-19 disease and then present the effect of flavonoids, which could help alleviate or eliminate complications in humans after overcoming the COVID-19 infection. Based on articles published from 2003 to 2021, we summarize the flavonoids-based molecular mechanisms associated with the post-COVID-19 syndrome and simultaneously provide a complex view regarding their prophylactic and therapeutic potential. Review clearly sorts out the outcome of post-COVID-19 syndrome according particular body systems. The conclusion is that flavonoids play an important role in prevention of many diseases. We suggest that flavonoids as critical nutritional supplements, are suitable for the alleviation and shortening of the period associated with the post-COVID-19 syndrome. The most promising flavonoid with noteworthy therapeutic and prophylactic effect appears to be quercetin.
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Affiliation(s)
- Annamária Bardelčíková
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
| | - Andrej Miroššay
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
| | - Jindřich Šoltýs
- Institute of Parasitology, Slovak Academy of Science, Košice, Slovak Republic
| | - Ján Mojžiš
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
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Ben Moftah M, Eswayah A. Intricate relationship between SARS-CoV-2-induced shedding and cytokine storm generation: A signaling inflammatory pathway augmenting COVID-19. HEALTH SCIENCES REVIEW (OXFORD, ENGLAND) 2022; 2:100011. [PMID: 35013738 PMCID: PMC8734057 DOI: 10.1016/j.hsr.2021.100011] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 12/20/2021] [Accepted: 12/29/2021] [Indexed: 12/24/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its ability to induce cytokine release syndrome, can set up a generalized inflammatory response together with activating multiple inflammatory pathways, which contributes to a dramatic increase in the number of mortalities and morbidities worldwide. Reportedly, the manipulative nature of coronavirus disease 2019 (COVID-19), which targets the immune system, often focuses on specific inflammation-related pathways, usually confined to interleukins and tumor necrosis factor-α (TNF-α), with a great emphasis on therapeutic approaches targeting the inhibition of these inflammatory mediators. The involvement of a disintegrin and metalloprotease 17 (ADAM-17) and matrix metalloproteinase-9 (MMP-9) in the pathogenesis of COVID-19, through their ability to potentiate the cytokine storm during an episode of SARS-CoV-2 infection, often goes unnoticed. In this review, the intricate relationship between ADAM-17 and MMP-9 together with angiotensin-converting enzyme 2 (ACE-2) as the main target for SARS-CoV-2 is highlighted in detail through a compilation of evidence-based literature; thus, we shed light on a proposed inflammatory pathway that COVID-19 may exploit to provoke an inflammatory response of a complex nature. Conclusively, our proposed mechanism acts as a means to developing a therapeutic approach aimed at modulating the intricate communication between ADAM-17 and MMP-9, where a great emphasis on the role of ACE-2 shedding and subsequent elevation in angiotensin II (Ang-II) levels is crucial to understanding the awry inflammatory response in patients with COVID-19. From this concept, designing a therapeutic strategy targeting multiple inflammatory mediators and enzymes simultaneously is another approach to unravel this global pandemic.
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Affiliation(s)
- Moayed Ben Moftah
- Department of Medicinal and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya
| | - Asma Eswayah
- Department of Medicinal and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya
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11
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Barkat MA, Kaushik P, Barkat HA, Khan MI, Hadi HA. Phytoconstituents in the Management of Covid-19: Demystifying the Fact. Drug Res (Stuttg) 2022; 72:123-130. [PMID: 34979573 DOI: 10.1055/a-1697-5365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The 2019-nCoV (COVID-19; novel coronavirus disease-2019) outbreak is caused by the coronavirus, and its continued spread is responsible for increasing deaths, social and economic burden. COVID-19 created a chaotic situation worldwide and claimed the lives of over 5,027,183 and 248,467,363 confirmed cases have been reported so far as per the data published by WHO (World Health Organization) till 5th November 2021. Scientific communities all over the world are toiling to find a suitable therapeutic drug for this deadly disease. Although till date no promising drug has been discovered for this COVID-19. However, as per the WHO, over 102 COVID-19 vaccines are in clinical development and 185 in pre-clinical development. Naturally occurring phytoconstituents possess considerable chemical richness in the form of anti-viral and anti-parasitic potential and have been extensively exploited for the same globally. Still, phytomedicine-based therapies are considered as the best available treatment option to minimize and treat the symptoms of COVID-19 because of the least possible side effects compared to synthetic drugs recommended by the physicians/clinicians. In this review, the use of plant chemicals as a possible therapeutic agent for severe acute respiratory syndrome coronavirus 2 (SARS CoV2) is highlighted with their proposed mechanism of action, which will prove fruitful and effective in finding a cure for this deadly disease.
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Affiliation(s)
- Md Abul Barkat
- Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, KSA
| | - Pawan Kaushik
- Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India
| | - Harshita Abul Barkat
- Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, KSA.,Dermatopharmaceutics Research Group, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
| | - Mohammad Idreesh Khan
- Department of Clinical Nutrition, College of Applied Health Sciences in Arras, Qassim University, KSA
| | - Hazrina Ab Hadi
- Dermatopharmaceutics Research Group, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
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Rahman MM, Ahmed M, Islam MT, Khan MR, Sultana S, Maeesa SK, Hasan S, Hossain MA, Ferdous KS, Mathew B, Rauf A, Uddin MS. Nanotechnology-based Approaches and Investigational Therapeutics against COVID-19. Curr Pharm Des 2022; 28:948-968. [PMID: 34218774 DOI: 10.2174/1381612827666210701150315] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 04/30/2021] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus responsible for the current global pandemic, which first emerged in December 2019. This coronavirus has affected 217 countries worldwide, most of which have enacted non-remedial preventive measures, such as nationwide lockdowns, work from home, travel bans, and social isolation. Pharmacists, doctors, nurses, technologists, and other healthcare professionals have played pivotal roles during this pandemic. Unfortunately, confirmed drugs have not been identified for the treatment of patients with coronavirus disease 2019 (COVID-19) caused by SARSCoV2; however, favipiravir and remdesivir have been reported as promising antiviral drugs. Some vaccines have already been developed, and vaccination is ongoing globally. Various nanotechnologies are currently being developed in many countries for preventing SARS-CoV-2 spread and treating COVID-19 infections. In this article, we present an overview of the COVID-19 pandemic situation and discuss nanotechnology-based approaches and investigational therapeutics for COVID-19.
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Affiliation(s)
- Md Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Muniruddin Ahmed
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Mohammad Touhidul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md Robin Khan
- Bangladesh Reference Institute for Chemical Measurements, Dhaka, Bangladesh
| | - Sharifa Sultana
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Saila Kabir Maeesa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Sakib Hasan
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md Abid Hossain
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Kazi Sayma Ferdous
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Bijo Mathew
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682041, India
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, Khyber Pakhtunkhwa, Pakistan
| | - Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
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13
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Al-Shuhaib MBS, Hashim HO, Al-Shuhaib JMB. Epicatechin is a promising novel inhibitor of SARS-CoV-2 entry by disrupting interactions between angiotensin-converting enzyme type 2 and the viral receptor binding domain: A computational/simulation study. Comput Biol Med 2021; 141:105155. [PMID: 34942397 PMCID: PMC8679518 DOI: 10.1016/j.compbiomed.2021.105155] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/15/2021] [Accepted: 12/15/2021] [Indexed: 01/02/2023]
Abstract
Angiotensin-converting enzyme 2 (ACE2) is the first target of SARS-CoV-2 and a key functional host receptor through which this virus hooks into and infects human cells. The necessity to block this receptor is one of the essential means to prevent the outbreak of COVID-19. This study was conducted to determine the most eligible natural compound to suppress ACE2 to counterfeit its interaction with the viral infection. To do this, the most known compounds of sixty-six Iraqi medicinal plants were generated and retrieved from PubChem database. After preparing a library for Iraqi medicinal plants, 3663 unique ligands’ conformers were docked to ACE2 using the GLIDE tool. Results found that twenty-three compounds exhibited the highest binding affinity with ACE2. The druglikeness and toxicity potentials of these compounds were evaluated using SwissADME and Protox servers respectively. Out of these virtually screened twenty-three compounds, epicatechin and kempferol were predicted to exert the highest druglikeness and lowest toxicity potentials. Extended Molecular dynamics (MD) simulations showed that ACE2-epicatechin complex exhibited a slightly higher binding stability than ACE2-kempferol complex. In addition to the well-known ACE2 inhibitors that were identified in previous studies, this study revealed for the first time that epicatechin from Hypericum perforatum provided a better static and dynamic inhibition for ACE2 with highly favourable pharmacokinetic properties than the other known ACE2 inhibiting compounds. This study entailed the ability of epicatechin to be used as a potent natural inhibitor that can be used to block or at least weaken the SARS-CoV-2 entry and its subsequent invasion. In vitro experiments are required to validate epicatechin effectiveness against the activity of the human ACE2 receptor.
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Affiliation(s)
- Mohammed Baqur S Al-Shuhaib
- Department of Animal Production, College of Agriculture, Al-Qasim Green University, Al-Qasim, 51013, Babil, Iraq.
| | - Hayder O Hashim
- Department of Clinical Laboratory Sciences, College of Pharmacy, University of Babylon, Babil, 51001, Iraq.
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14
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Caliskan UK, Karakus MM. Evaluation of botanicals as potential COVID-19 symptoms terminator. World J Gastroenterol 2021; 27:6551-6571. [PMID: 34754152 PMCID: PMC8554406 DOI: 10.3748/wjg.v27.i39.6551] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/01/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Information about the coronavirus disease 2019 (COVID-19) pandemic is still evolving since its appearance in December 2019 and has affected the whole world. Particularly, a search for an effective and safe treatment for COVID-19 continues. Botanical mixtures contain secondary metabolites (such as flavonoids, phenolics, alkaloids, essential oils etc.) with many therapeutic effects. In this study, the use of herbal treatments against COVID-19 was evaluated. Medical synthetic drugs focus mainly on respiratory symptoms, however herbal therapy with plant extracts may be useful to relieve overall symptoms of COVID-19 due to the variety of bioactive ingredients. Since COVID-19 is a virus that affects the respiratory tract, the antiviral effects of botanicals/plants against respiratory viruses have been examined through clinical studies. Data about COVID-19 patients revealed that the virus not only affects the respiratory system but different organs including the gastrointestinal (GI) system. As GI symptoms seriously affect quality of life, herbal options that might eliminate these problems were also evaluated. Finally, computer modeling studies of plants and their active compounds on COVID-19 were included. In summary, herbal therapies were identified as potential options for both antiviral effects and control of COVID-19 symptoms. Further data will be needed to enlighten all aspects of COVID-19 pathogenesis, before determining the effects of plants on severe acute respiratory syndrome coronavirus 2.
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Affiliation(s)
- Ufuk Koca Caliskan
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
| | - Methiye Mancak Karakus
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
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15
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Isaac-Lam MF. Molecular modeling of the interaction of ligands with ACE2-SARS-CoV-2 spike protein complex. In Silico Pharmacol 2021; 9:55. [PMID: 34631362 PMCID: PMC8495439 DOI: 10.1007/s40203-021-00114-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 09/28/2021] [Indexed: 02/06/2023] Open
Abstract
COVID-19 is a new communicable disease with a widespread outbreak that affects all populations worldwide triggering a rush of scientific interest in coronavirus research globally. In silico molecular docking experiment was utilized to determine interactions of available compounds with SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) complex. Chimera and AutoDock Vina were used for protein-ligand interaction structural analysis. Ligands were chosen based on the known characteristics and indications of the drugs as ACE inhibitors (captopril, enalapril, quinapril, moexipril, benazepril, ramipril, perindopril, zofenopril, fosinopril), as ACE2 blockers (losartan, olmesartan), as blood thinning agent (clopidogrel), as cholesterol-lowering prescriptions (simvastatin, atorvastatin), repurposed medications (dexamethasone, hydroxychloroquine, chloroquine), and as investigational drug (remdesivir). Experimental ACE/ACE2 inhibitors are also included: Sigma ACEI, N-(2-aminoethyl)-1-aziridine-ethanamine (NAAE), nicotianamine (NAM), and MLN-4760 (ACE2 inhibitor). The best docked conformations were all located in the ACE2 protein, 50% docked at the interface with lower scores and only clopidogrel and hydroxychloroquine docked at the spike protein. Captopril, moexipril, benazepril, fosinopril, losartan, remdesivir, Sigma ACEI, NAA, and NAM interacted and docked at the interface of ACE2 and SARS-CoV-2 spike protein complex. This may have significant implication in enhancing our understanding of the mechanism to hinder viral entry into the host organism during infection. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s40203-021-00114-w.
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Affiliation(s)
- Meden F. Isaac-Lam
- Department of Chemistry and Physics, Purdue University Northwest, Westville, IN 46391 USA
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16
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Chandramouli V, Niraj SK, Nair KG, Joseph J, Aruni W. Phytomolecules Repurposed as Covid-19 Inhibitors: Opportunity and Challenges. Curr Microbiol 2021; 78:3620-3633. [PMID: 34448061 PMCID: PMC8390070 DOI: 10.1007/s00284-021-02639-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 08/20/2021] [Indexed: 12/29/2022]
Abstract
The SARS-CoV-2 virus has spread worldwide to cause a full blown pandemic since 2020. To date, several promising synthetic therapeutics are repurposed and vaccines through different stages of clinical trials were approved and being administered, but still the efficacy of the drugs and vaccines are yet to be decoded. This article highlights the importance of traditional medicinal plants and the phytomolecules derived from them, which possess in vitro antiviral and anti-CoV properties and further explores their potential as inhibitors to molecular targets of SARS-CoV-2 that were evaluated by in silico approaches. Botanicals in traditional medicinal systems have been investigated for anti-SARS-CoV-2 activity through in silico and in vitro studies. However, information linking structure of phytomolecules to their antiviral activity is limited. Most phytomolecules with anti-CoV activity were studied for inhibition of the human ACE2 receptor through which the virus enters host cells, and non-structural proteins 3CLpro and PLpro. Although the proteases are ideal anti-CoV targets, information on plant-based inhibitors for the CoV structural proteins, e.g., spike, envelope, membrane, nucleocapsid required further investigations. In absence of scientific evaluations through in vitro and biocompatibility studies, plant-based antivirals fall short as treatment options. Plant-based anti-SARS-CoV-2 therapeutics can be promising alternatives to their synthetic counterparts as they are economical and bear fewer chances of toxicity, side effects, and viral resistance. Our review could provide a systematic overview of the potential phytomolecules which can be repurposed and subjected to further modes of experimental evaluation to qualify for use in treatment and prophylaxis of SARS-CoV-2 infections.
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Affiliation(s)
- Vaishnavi Chandramouli
- Advanced Institute for Wildlife Conservation, Tamil Nadu Forest Department, Government of Tamil Nadu, Chennai, 600048, India
| | - Shekhar Kumar Niraj
- Advanced Institute for Wildlife Conservation, Tamil Nadu Forest Department, Government of Tamil Nadu, Chennai, 600048, India
| | - Krishna G Nair
- MES T O Abdulla Memorial College, Kunnukara, Aluva, Kerala, 683578, India
| | - Jerrine Joseph
- Centre for Drug Discovery and Development, Sathyabama Institute of Science and Technology, Chennai, 600119, India.
| | - Wilson Aruni
- Sathyabama Institute of Science and Technology, Chennai, 600119, India
- School of Medicine, Loma Linda University, Loma Linda, CA, USA
- Musculoskeletal Disease Research Laboratory US, Department of Veteran Affairs, Loma Linda, CA, USA
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17
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Saied AA, Metwally AA, Madkhali NAB, Haque S, Dhama K. Egypt's COVID-19 Recent Happenings and Perspectives: A Mini-Review. Front Public Health 2021; 9:696082. [PMID: 34485226 PMCID: PMC8415352 DOI: 10.3389/fpubh.2021.696082] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/12/2021] [Indexed: 01/08/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected countries across the world. While the zoonotic aspects of SARS-CoV-2 are still under investigation, bats and pangolins are currently cited as the animal origin of the virus. Several types of vaccines against COVID-19 have been developed and are being used in vaccination drives across the world. A number of countries are experiencing second and third waves of the pandemic, which have claimed nearly four million lives out of the 180 million people infected globally as of June 2021. The emerging SARS-CoV-2 variants and mutants are posing high public health concerns owing to their rapid transmissibility, higher severity, and in some cases, ability to infect vaccinated people (vaccine breakthrough). Here in this mini-review, we specifically looked at the efforts and actions of the Egyptian government to slow down and control the spread of COVID-19. We also review the COVID-19 statistics in Egypt and the possible reasons behind the low prevalence and high case fatality rate (CFR%), comparing Egypt COVID-19 statistics with China (the epicenter of COVID-19 pandemic) and the USA, Brazil, India, Italy, and France (the first countries in which the numbers of patients infected with COVID-19). Additionally, we have summarized the SARS-CoV-2 variants, vaccines used in Egypt, and the use of medicinal plants as preventive and curative options.
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Affiliation(s)
- AbdulRahman A Saied
- Department of Food Establishments Licensing (Aswan Branch), National Food Safety Authority (NFSA), Aswan, Egypt.,Touristic Activities and Interior Offices Sector (Aswan Office), Ministry of Tourism and Antiquities, Aswan, Egypt
| | - Asmaa A Metwally
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Aswan University, Aswan, Egypt
| | | | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.,Bursa Uludağ University, Faculty of Medicine, Bursa, Turkey
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
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18
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Flores-Félix JD, Gonçalves AC, Alves G, Silva LR. Consumption of Phenolic-Rich Food and Dietary Supplements as a Key Tool in SARS-CoV-19 Infection. Foods 2021; 10:2084. [PMID: 34574194 PMCID: PMC8469666 DOI: 10.3390/foods10092084] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/29/2021] [Accepted: 09/02/2021] [Indexed: 12/23/2022] Open
Abstract
The first cases of COVID-19, which is caused by the SARS-CoV-2, were reported in December 2019. The vertiginous worldwide expansion of SARS-CoV-2 caused the collapse of health systems in several countries due to the high severity of the COVID-19. In addition to the vaccines, the search for active compounds capable of preventing and/or fighting the infection has been the main direction of research. Since the beginning of this pandemic, some evidence has highlighted the importance of a phenolic-rich diet as a strategy to reduce the progression of this disease, including the severity of the symptoms. Some of these compounds (e.g., curcumin, gallic acid or quercetin) already showed capacity to limit the infection of viruses by inhibiting entry into the cell through its binding to protein Spike, regulating the expression of angiotensin-converting enzyme 2, disrupting the replication in cells by inhibition of viral proteases, and/or suppressing and modulating the host's immune response. Therefore, this review intends to discuss the most recent findings on the potential of phenolics to prevent SARS-CoV-2.
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Affiliation(s)
- José David Flores-Félix
- CICS-UBI–Health Sciences Research Centre, Faculty of Health Science, University of Beira Interior, 6200-506 Covilhã, Portugal; (J.D.F.-F.); (A.C.G.); (G.A.)
| | - Ana C. Gonçalves
- CICS-UBI–Health Sciences Research Centre, Faculty of Health Science, University of Beira Interior, 6200-506 Covilhã, Portugal; (J.D.F.-F.); (A.C.G.); (G.A.)
| | - Gilberto Alves
- CICS-UBI–Health Sciences Research Centre, Faculty of Health Science, University of Beira Interior, 6200-506 Covilhã, Portugal; (J.D.F.-F.); (A.C.G.); (G.A.)
| | - Luís R. Silva
- CICS-UBI–Health Sciences Research Centre, Faculty of Health Science, University of Beira Interior, 6200-506 Covilhã, Portugal; (J.D.F.-F.); (A.C.G.); (G.A.)
- Unidade de Investigação para o Desenvolvimento do Interior (UDI/IPG), Instituto Politécnico da Guarda, 6300-559 Guarda, Portugal
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19
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Farshi P, Kaya EC, Hashempour-Baltork F, Khosravi-Darani K. The effect of plant metabolites on coronaviruses: A comprehensive review focusing on their IC50 values and molecular docking scores. Mini Rev Med Chem 2021; 22:457-483. [PMID: 34488609 DOI: 10.2174/1389557521666210831152511] [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: 08/17/2020] [Revised: 03/10/2021] [Accepted: 06/29/2021] [Indexed: 01/08/2023]
Abstract
Coronaviruses have caused worldwide outbreaks in different periods. SARS (severe acute respiratory syndrome), was the first emerged virus from this family, followed by MERS (Middle East respiratory syndrome) and SARS-CoV-2 (2019-nCoV or COVID 19), which is newly emerged. Many studies have been conducted on the application of chemical and natural drugs for treating these coronaviruses and they are mostly focused on inhibiting the proteases of viruses or blocking their protein receptors through binding to amino acid residues. Among many substances which are introduced to have an inhibitory effect against coronaviruses through the mentioned pathways, natural components are of specific interest. Secondary and primary metabolites from plants, are considered as potential drugs to have an inhibitory effect on coronaviruses. IC50 value (the concentration in which there is 50% loss in enzyme activity), molecular docking score and binding energy are parameters to understand the ability of metabolites to inhibit the specific virus. In this study we did a review of 154 papers on the effect of plant metabolites on different coronaviruses and data of their IC50 values, molecular docking scores and inhibition percentages are collected in tables. Secondary plant metabolites such as polyphenol, alkaloids, terpenoids, organosulfur compounds, saponins and saikosaponins, lectins, essential oil, and nicotianamine, and primary metabolites such as vitamins are included in this study.
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Affiliation(s)
- Parastou Farshi
- Food Science Institute, Kansas State University, Manhattan, Kansas. United States
| | - Eda Ceren Kaya
- Food Science Institute, Kansas State University, Manhattan, Kansas. United States
| | - Fataneh Hashempour-Baltork
- Student Research Committee, Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran. Iran
| | - Kianoush Khosravi-Darani
- Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran. Iran
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20
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Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19? Adv Biol Regul 2021; 81:100820. [PMID: 34419773 PMCID: PMC8359569 DOI: 10.1016/j.jbior.2021.100820] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/05/2021] [Accepted: 08/09/2021] [Indexed: 12/15/2022]
Abstract
The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several “converging” evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1–7 and Ang 1–9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.
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21
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Chen W, Wang Z, Wang Y, Li Y. Natural Bioactive Molecules as Potential Agents Against SARS-CoV-2. Front Pharmacol 2021; 12:702472. [PMID: 34483904 PMCID: PMC8416071 DOI: 10.3389/fphar.2021.702472] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 07/12/2021] [Indexed: 12/24/2022] Open
Abstract
In the past two decades, pandemics of several fatal coronaviruses have posed enormous challenges for public health, including SARS-CoV (2003), MERS-CoV (2012), and SARS-CoV-2 (2019). Among these, SARS-CoV-2 continues to ravage the world today and has lead to millions of deaths and incalculable economic damage. Till now, there is no clinically proven antiviral drug available for SARS-CoV-2. However, the bioactive molecules of natural origin, especially medicinal plants, have been proven to be potential resources in the treatment of SARS-CoV-2, acting at different stages of the viral life cycle and targeting different viral or host proteins, such as PLpro, 3CLpro, RdRp, helicase, spike, ACE2, and TMPRSS2. They provide a viable strategy to develop therapeutic agents. This review presents fundamental biological information on SARS-CoV-2, including the viral biological characteristics and invasion mechanisms. It also summarizes the reported natural bioactive molecules with anti-coronavirus properties, arranged by their different targets in the life cycle of viral infection of human cells, and discusses the prospects of these bioactive molecules for the treatment of COVID-19.
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Affiliation(s)
- Wei Chen
- Department of Medicinal Chemistry, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
| | - Zhihao Wang
- Biobank, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yawen Wang
- Biobank, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Laboratory Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yiping Li
- Department of Medicinal Chemistry, School of Pharmacy, Xi’an Jiaotong University, Xi’an, China
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22
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Mohammadi Pour P, Farzaei MH, Soleiman Dehkordi E, Bishayee A, Asgary S. Therapeutic targets of natural products for the management of cardiovascular symptoms of coronavirus disease 2019. Phytother Res 2021; 35:5417-5426. [PMID: 34110678 DOI: 10.1002/ptr.7172] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 03/01/2021] [Accepted: 04/09/2021] [Indexed: 12/14/2022]
Abstract
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first occurred in China in December 2019 and subsequently spread all over the world with cardiovascular, renal, and pulmonary symptoms. Therefore, recognizing and treating the cardiovascular sign and symptoms that caused by coronavirus disease 2019 (COVID-19) can be effective in reducing patient mortality. To control the COVID-19-related cardiovascular symptoms, natural products are considered one of the promising choices as complementary medicine. Scientists are struggling to discover new antiviral agents specific to this virus. In this review, the natural products for management of cardiovascular symptoms of COVID-19 are categorized into three groups: (a) natural products with an impact on angiotensin II type 1 receptor; (b) natural products that inhibit angiotensin-converting enzyme activity; and (c) natural products that mimic adenosine activity. All these natural products should undergo clinical investigations to test their efficacy, safety, and toxicity in the treatment of cardiovascular symptoms of COVID-19. This article summarizes agents with potential efficacy against COVID-19-related cardiovascular symptoms.
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Affiliation(s)
- Pardis Mohammadi Pour
- Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ebrahim Soleiman Dehkordi
- Medical Plants Research Center, Basic Health Science, Shahrekord University of Medical Science, Shahrekord, Iran
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Sedigheh Asgary
- Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
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23
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Abubakar MB, Usman D, El-Saber Batiha G, Cruz-Martins N, Malami I, Ibrahim KG, Abubakar B, Bello MB, Muhammad A, Gan SH, Dabai AI, Alblihed M, Ghosh A, Badr RH, Thangadurai D, Imam MU. Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies. Front Pharmacol 2021; 12:629935. [PMID: 34012391 PMCID: PMC8126690 DOI: 10.3389/fphar.2021.629935] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 03/08/2021] [Indexed: 01/08/2023] Open
Abstract
The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.
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Affiliation(s)
- Murtala Bello Abubakar
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Dawoud Usman
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Ibrahim Malami
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
- Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Kasimu Ghandi Ibrahim
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Bilyaminu Abubakar
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
- Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Muhammad Bashir Bello
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
- Department of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Aliyu Muhammad
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna Sate, Nigeria
| | - Siew Hua Gan
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Aliyu Ibrahim Dabai
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
- Department of Microbiology, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - M Alblihed
- Department of Microbiology, College of Medicine, Taif University, Taif, Saudi Arabia
| | - Arabinda Ghosh
- Microbiology Division, Department of Botany, Gauhati University, Guwahati, India
| | - Reem H. Badr
- Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria, Egypt
| | | | - Mustapha Umar Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria
- Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
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Marmitt DJ, Goettert MI, Rempel C. Compounds of plants with activity against SARS-CoV-2 targets. Expert Rev Clin Pharmacol 2021; 14:623-633. [PMID: 33706626 PMCID: PMC8022338 DOI: 10.1080/17512433.2021.1903317] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The COVID-19 global pandemic is a public health emergency due to its high virulence and mortality. Many vaccine development studies at clinical trials are currently conducted to combat SARS-CoV-2. Plants are a rich source of phytochemicals with different biological activities, including antiviral activities, which are the focus of many studies. AREAS COVERED This review shows compounds of traditional plants listed on RENISUS list have therapeutic properties against SARS-CoV-2 targets. EXPERT OPINION The rise of new variants, more pathogenic and virulent, impacts in the increase of mortality from SARS-CoV-2 infection, and thus, the control of the outbreaks of disease remains a global challenge. Other's drug and vaccines development is an essential element in controlling SARS-COV-2. Therefore, it is imperative that approach to tackle this pandemic has to be solidly evidence-informed. It should be noticed that the immune system does play critical roles in fighting viruses. Studies show that T cells levels decreased continuously as the disease progressed. T cell-mediated cellular immune response, probably by immunological memory, is essential for direct virus eradication after infection whilst B cells functions in producing antibodies that neutralize virus.But, have distinct patterns of T cell response exist in different patients, suggesting the possibility of distinct clinical approaches. Efforts are concentrated to elucidate the underlying immunological mechanisms in SARS-CoV-2 pathogenesis and progression for better design of diagnostic, therapeutic and preventive strategies. We seek to identify biomolecules with the potential to act in biomarkers that predict how severe the disease can get. But it is important to warn that the plants that produce the compounds mentioned here should not be used without a physician prescription. Finally, we speculate that these compounds may eventually attract the attention of physicians and researchers to perform tests in specific contexts of SARS-CoV-2 infection, and if they show positive results, be tested in Clinical trials.
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Affiliation(s)
- Diorge Jônatas Marmitt
- Programa De Pós-graduação Em Biotecnologia, Universidade Do Vale Do Taquari - Univates, Lajeado RS, Brazil
| | - Márcia Inês Goettert
- Programa De Pós-graduação Em Biotecnologia, Universidade Do Vale Do Taquari - Univates, Lajeado RS, Brazil
| | - Claudete Rempel
- Programa De Pós-graduação Em Ambiente E Desenvolvimento/Programa De Pós-graduação Em Sistemas Ambientais Sustentáveis, Universidade Do Vale Do Taquari – Univates , Lajeado RS, Brazil
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Oz M, Lorke DE, Kabbani N. A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor. Pharmacol Ther 2021; 221:107750. [PMID: 33275999 PMCID: PMC7854082 DOI: 10.1016/j.pharmthera.2020.107750] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/18/2020] [Accepted: 11/19/2020] [Indexed: 02/06/2023]
Abstract
The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.
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Key Words
- adam17, a disintegrin and metalloprotease 17
- ace, angiotensin i converting enzyme
- ace-inh., angiotensin i converting enzyme inhibitor
- ampk, amp-activated protein kinase
- ang-ii, angiotensin ii
- arb, angiotensin ii type 1-receptor blocker
- ards, acute respiratory distress syndrome
- at1-r, angiotensin ii type 1-receptor
- βarb, β-adrenergic receptor blockers
- bk, bradykinin
- ccb, calcium channel blockers
- ch25h, cholesterol-25-hydroxylase
- copd, chronic obstructive lung disease
- cox, cyclooxygenase
- covid-19, coronavirus disease-2019
- dabk, [des-arg9]-bradykinin
- erk, extracellular signal-regulated kinase
- 25hc, 25-hydroxycholesterol
- hs, heparan sulfate
- hspg, heparan sulfate proteoglycan
- ibd, inflammatory bowel disease
- map, mitogen-activated protein
- mers, middle east respiratory syndrome
- mrb, mineralocorticoid receptor blocker
- nos, nitric oxide synthase
- nsaid, non-steroid anti-inflammatory drug
- ras, renin-angiotensin system
- sars-cov, severe acute respiratory syndrome coronavirus
- sh, spontaneously hypertensive
- s protein, spike protein
- sirt1, sirtuin 1
- t2dm, type 2 diabetes mellitus
- tcm, traditional chinese medicine
- tmprss2, transmembrane protease, serine 2
- tnf, tumor necrosis factor
- ufh, unfractionated heparin
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Affiliation(s)
- Murat Oz
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat 13110, Kuwait.
| | - Dietrich Ernst Lorke
- Department of Anatomy and Cellular Biology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Nadine Kabbani
- School of Systems Biology, George Mason University, Fairfax, VA 22030, USA
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Nayak SK. Inhibition of S-protein RBD and hACE2 Interaction for Control of SARSCoV- 2 Infection (COVID-19). Mini Rev Med Chem 2021; 21:689-703. [PMID: 33208074 DOI: 10.2174/1389557520666201117111259] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 08/25/2020] [Accepted: 09/05/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND COVID-19 has become a pandemic with higher morbidity and mortality rates after its start from Wuhan city of China. The infection by RNA virus, also known as SARS-CoV-2 or 2019-nCoV, from the beta class of coronaviruses, has been found to be responsible for COVID-19. Structural analysis and evidences have been indicated that interaction between a segment of receptor binding domain (RBD) from S protein of the virus and human angiotensin-converting enzyme 2 (hACE2) is essential for cellular entry of the virus. OBJECTIVE The current review sheds light on structural aspects for the inhibition of RBD-hACE2 interaction mediated cellular entry of SARS-CoV-2. METHODS The present study provides a critical review of recently published information on RBDhACE2 interaction and its inhibitors to control SARS-CoV-2 infection. The review highlighted the structural aspects of the interaction between RBD-hACE2 and involved amino acid residues. RESULTS Recently, several studies are being conducted for the inhibition of the SARS-CoV-2 attachment and entry to the human cellular system. One of the important targets for viral invasion is its binding with cell surface receptor, hACE2, through RBD on S-protein. Mimicking of three residues on ACE2 (Lys31, Glu35 and Lys353 on B chain) provided a hot target directed strategy for the inhibition of early attachment of the virus to the cell. Early screening of peptidic or non-peptidic molecules for the inhibition of RBD-hACE2 interaction has raised the hope for potential therapeutics against COVID-19. The higher affinity of molecules toward RBD than ACE2 is an important factor for selectivity and minimization of ACE2 related adverse events on the cardiovascular system, brain, kidney, and foetus development during pregnancy. CONCLUSION Inhibition of RBD-hACE2 interaction by different molecular scaffolds can be used as a preferred strategy for control of SARS-CoV-2 infection. Recently, published reports pointed out Lys31, Glu35 and Lys353 on the B chain of ACE2 as crucial residues for mimicking and design of novel molecules as inhibitors SARS-CoV-2 attachment to human cells. Moreover, some recently identified RBD-hACE2 interaction inhibitors have also been described with their protein binding pattern and potencies (IC50 values), which will help for further improvement in the selectivity.
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Affiliation(s)
- Surendra Kumar Nayak
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar- Delhi G.T. Road (NH-1), Phagwara, Punjab-144401, India
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Keflie TS, Biesalski HK. Micronutrients and bioactive substances: Their potential roles in combating COVID-19. Nutrition 2021; 84:111103. [PMID: 33450678 PMCID: PMC7717879 DOI: 10.1016/j.nut.2020.111103] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 11/11/2020] [Accepted: 11/30/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES The coronavirus disease 2019 (COVID-19) pandemic is seriously threatening public health and setting off huge economic crises across the world. In the absence of specific drugs for COVID-19, there is an urgent need to look for alternative approaches. Therefore, the aim of this paper was to review the roles of micronutrients and bioactive substances as potential alternative approaches in combating COVID-19. METHODS This review was based on the literature identified using electronic searches in different databases. RESULTS Vitamins (A, B, C, D, and E), minerals (selenium and zinc), and bioactive substances from curcumin, echinacea, propolis, garlic, soybean, green tea, and other polyphenols were identified as having potential roles in interfering with spike glycoproteins, angiotensin converting enzyme 2, and transmembrane protease serine 2 at the entry site, and inhibiting activities of papain-like protease, 3 chymotrypsin-like protease, and RNA-dependent RNA polymerase in the replication cycle of severe acute respiratory syndrome coronavirus 2. Having immunomodulating, antiinflammatory, antioxidant, and antiviral properties, such micronutrients and bioactive substances are consequently promising alterative nutritional approaches to combat COVID-19. CONCLUSIONS The roles of micronutrients and bioactive substances in the fight against COVID-19 are exciting areas of research. This review may suggest directions for further study.
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Oz M, Lorke DE. Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury. Biomed Pharmacother 2021; 136:111193. [PMID: 33461019 PMCID: PMC7836742 DOI: 10.1016/j.biopha.2020.111193] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 12/15/2020] [Accepted: 12/26/2020] [Indexed: 12/11/2022] Open
Abstract
The recent emergence of coronavirus disease-2019 (COVID-19) as a pandemic affecting millions of individuals has raised great concern throughout the world, and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was identified as the causative agent for COVID-19. The multifunctional protein angiotensin converting enzyme 2 (ACE2) is accepted as its primary target for entry into host cells. In its enzymatic function, ACE2, like its homologue ACE, regulates the renin-angiotensin system (RAS) critical for cardiovascular and renal homeostasis in mammals. Unlike ACE, however, ACE2 drives an alternative RAS pathway by degrading Ang-II and thus operates to balance RAS homeostasis in the context of hypertension, heart failure, and cardiovascular as well as renal complications of diabetes. Outside the RAS, ACE2 hydrolyzes key peptides, such as amyloid-β, apelin, and [des-Arg9]-bradykinin. In addition to its enzymatic functions, ACE2 is found to regulate intestinal amino acid homeostasis and the gut microbiome. Although the non-enzymatic function of ACE2 as the entry receptor for SARS-CoV-2 has been well established, the contribution of enzymatic functions of ACE2 to the pathogenesis of COVID-19-related lung injury has been a matter of debate. A complete understanding of this central enzyme may begin to explain the various symptoms and pathologies seen in SARS-CoV-2 infected individuals, and may aid in the development of novel treatments for COVID-19.
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Affiliation(s)
- Murat Oz
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat 13110, Kuwait.
| | - Dietrich Ernst Lorke
- Department of Anatomy and Cellular Biology, Khalifa University, Abu Dhabi, United Arab Emirates; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
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Shahid M, Shahzad-Ul-Hussan S. Structural insights of key enzymes into therapeutic intervention against SARS-CoV-2. J Struct Biol 2021; 213:107690. [PMID: 33383190 PMCID: PMC7769706 DOI: 10.1016/j.jsb.2020.107690] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 12/03/2020] [Accepted: 12/23/2020] [Indexed: 01/18/2023]
Abstract
COVID-19 pandemic, caused by SARS-CoV-2, has drastically affected human health all over the world. After the emergence of the pandemic the major focus of efforts to attenuate the infection has been on repurposing the already approved drugs to treat COVID-19 adopting a fast-track strategy. However, to date a specific regimen to treat COVID-19 is not available. Over the last few months a substantial amount of data about the structures of various key proteins and their recognition partners involved in the SARS-CoV-2 pathogenesis has emerged. These studies have not only provided the molecular level descriptions ofthe viral pathogenesis but also laid the foundation for rational drug design and discovery. In this review, we have recapitulated the structural details of four key viral enzymes, RNA-dependent RNA polymerase, 3-chymotrypsin like protease, papain-like protease and helicase, and two host factors including angiotensin-converting enzyme 2 and transmembrane serine protease involved in the SARS-CoV-2 pathogenesis, and described the potential hotspots present on these structures which could be explored for therapeutic intervention. We have also discussed the significance of endoplasmic reticulum α-glucosidases as potential targets for anti-SARS-CoV-2 drug discovery.
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Affiliation(s)
- Munazza Shahid
- Department of Biology, SBA School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan
| | - Syed Shahzad-Ul-Hussan
- Department of Biology, SBA School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan.
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Illian DN, Siregar ES, Sumaiyah S, Utomo AR, Nuryawan A, Basyuni M. Potential compounds from several Indonesian plants to prevent SARS-CoV-2 infection: A mini-review of SARS-CoV-2 therapeutic targets. Heliyon 2021; 7:e06001. [PMID: 33532640 PMCID: PMC7833933 DOI: 10.1016/j.heliyon.2021.e06001] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/31/2020] [Accepted: 01/13/2021] [Indexed: 12/19/2022] Open
Abstract
The outbreak of coronaviruses (CoVs) presents an enormous threat to humans. To date, no new therapeutic drugs or vaccines licensed to treat human coronaviruses remain undiscovered. This mini-review briefly reports the number of potential plants widely distributed in Indonesia for further research and development as anti-SARS-CoV-2 agents and the critical targets for SARS-CoV-2 therapy, such as angiotensin-converting enzyme 2 (ACE-2) receptor, spike protein, 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), helicase, and serine protease. Indonesia is rich in medicinal plants (herbal); it also has a long history of using plants to treat various hereditary diseases. However, since SARS-CoV-2 is a new disease, it has no history of plant-based treatment anywhere in the world. This mini-review describes natural products from several Indonesian plants that contain compounds that could potentially prevent or reduce SARS-CoV-2 infection, act as potential targeted therapy, and provide new therapeutic strategies to develop SARS-CoV-2 countermeasures.
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Affiliation(s)
- Didi Nurhadi Illian
- Department of Pharmacy, Faculty of Mathematics and Natural Science, Universitas Syiah Kuala, Banda Aceh, 23111, Indonesia
| | - Etti Sartina Siregar
- Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, 20155, Indonesia.,Center of Excellence for Mangrove, Universitas Sumatera Utara, Medan, 20155, Indonesia
| | - Sumaiyah Sumaiyah
- Department of Technology Pharmacy, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia
| | - Ahmad Rusdan Utomo
- Senior Molecular Testing Laboratory Consultant at Clinical Lab Advisor, Indonesia.,Perhimpunan Biologi Medik Indonesia PBMI, Indonesia
| | - Arif Nuryawan
- Department of Forestry, Faculty of Forestry, Universitas Sumatera Utara, Medan, 20155, Indonesia.,Center of Excellence for Mangrove, Universitas Sumatera Utara, Medan, 20155, Indonesia
| | - Mohammad Basyuni
- Department of Forestry, Faculty of Forestry, Universitas Sumatera Utara, Medan, 20155, Indonesia.,Center of Excellence for Mangrove, Universitas Sumatera Utara, Medan, 20155, Indonesia
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Laws M, Surani YM, Hasan MM, Chen Y, Jin P, Al-Adhami T, Chowdhury M, Imran A, Psaltis I, Jamshidi S, Nahar KS, Rahman KM. Current Trends and Future Approaches in Small-Molecule Therapeutics for COVID-19. Curr Med Chem 2021; 28:3803-3824. [PMID: 32693756 PMCID: PMC7611096 DOI: 10.2174/0929867327666200721161840] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/29/2020] [Accepted: 06/30/2020] [Indexed: 02/06/2023]
Abstract
The novel coronavirus (SARS-CoV-2) pandemic has created a global public health emergency. The pandemic is causing substantial morbidity, mortality and significant economic loss. Currently, no approved treatments for COVID-19 are available, and it is likely to takes at least 12-18 months to develop a new vaccine. Therefore, there is an urgent need to find new therapeutics that can be progressed to clinical development as soon as possible. Repurposing regulatory agency-approved drugs and experimental drugs with known safety profiles can provide important repositories of compounds that can be fast-tracked to clinical development. Globally, over 500 clinical trials involving repurposed drugs have been registered, and over 150 have been initiated, including some backed by the World Health Organisation (WHO). This review is intended as a guide to research into small-molecule therapies to treat COVID-19; it discusses the SARS-CoV-2 infection cycle and identifies promising viral therapeutic targets, reports on a number of promising pre-approved small-molecule drugs with reference to over 150 clinical trials worldwide, and offers a perspective on the future of the field.
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Affiliation(s)
- Mark Laws
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Yasmin M. Surani
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Md. Mahbub Hasan
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Yiyuan Chen
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Peiqin Jin
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Taha Al-Adhami
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Madiha Chowdhury
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Aqeel Imran
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Ioannis Psaltis
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Shirin Jamshidi
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Kazi S. Nahar
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Khondaker Miraz Rahman
- Institute of Pharmaceutical Sciences, School of Cancer and Pharmaceutical Sciences, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
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Neumaier F, Zlatopolskiy BD, Neumaier B. Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics. Pharmaceutics 2020; 12:E1247. [PMID: 33371500 PMCID: PMC7767508 DOI: 10.3390/pharmaceutics12121247] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 12/15/2020] [Accepted: 12/17/2020] [Indexed: 02/06/2023] Open
Abstract
The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular level and for treatment approaches based on targeted delivery of therapeutic radionuclides. Ongoing development of radiolabeling methods has significantly improved the accessibility of radiopharmaceuticals for in vivo molecular imaging or targeted radionuclide therapy, but their use for biosafety threats such as SARS-CoV-2 is restricted by the contagious nature of these agents. Here, we highlight several potential uses of nuclear medicine in the context of SARS-CoV-2 and COVID-19, many of which could also be performed in laboratories without dedicated containment measures. In addition, we provide a broad overview of experimental or repurposed SARS-CoV-2-targeting drugs and describe how radiolabeled analogs of these compounds could facilitate antiviral drug development and translation to the clinic, reduce the incidence of late-stage failures and possibly provide the basis for radionuclide-based treatment strategies. Based on the continuing threat by emerging coronaviruses and other pathogens, it is anticipated that these applications of nuclear medicine will become a more important part of future antiviral drug development and treatment.
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Affiliation(s)
- Felix Neumaier
- Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, Germany; (B.D.Z.); (B.N.)
- Institute of Radiochemistry and Experimental Molecular Imaging, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
| | - Boris D. Zlatopolskiy
- Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, Germany; (B.D.Z.); (B.N.)
- Institute of Radiochemistry and Experimental Molecular Imaging, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
- Max Planck Institute for Metabolism Research, 50931 Cologne, Germany
| | - Bernd Neumaier
- Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, Germany; (B.D.Z.); (B.N.)
- Institute of Radiochemistry and Experimental Molecular Imaging, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
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Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules. Pharmaceuticals (Basel) 2020; 13:ph13120447. [PMID: 33302344 PMCID: PMC7762362 DOI: 10.3390/ph13120447] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/05/2020] [Accepted: 11/12/2020] [Indexed: 12/17/2022] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus belonging to the Coronavirus family, is now known to cause Coronavirus Disease (Covid-19) which was first recognized in December 2019. Covid-19 leads to respiratory illnesses ranging from mild infections to pneumonia and lung failure. Strikingly, within a few months of its first report, Covid-19 has spread worldwide at an exceptionally high speed and it has caused enormous human casualties. As yet, there is no specific treatment for Covid-19. Designing inhibitory drugs that can interfere with the viral entry process constitutes one of the main preventative therapies that could combat SARS-CoV-2 infection at an early stage. In this review, we provide a brief introduction of the main features of coronaviruses, discuss the entering mechanism of SARS-CoV-2 into human host cells and review small molecules that inhibit SARS-CoV-2 entry into host cells. Specifically, we focus on small molecules, identified by experimental validation and/or computational prediction, that target the SARS-CoV-2 spike protein, human angiotensin converting enzyme 2 (ACE2) receptor and the different host cell proteases that activate viral fusion. Given the persistent rise in Covid-19 cases to date, efforts should be directed towards validating the therapeutic effectiveness of these identified small molecule inhibitors.
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Liu X, Raghuvanshi R, Ceylan FD, Bolling BW. Quercetin and Its Metabolites Inhibit Recombinant Human Angiotensin-Converting Enzyme 2 (ACE2) Activity. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:13982-13989. [PMID: 33179911 PMCID: PMC7687294 DOI: 10.1021/acs.jafc.0c05064] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 10/21/2020] [Accepted: 10/31/2020] [Indexed: 05/02/2023]
Abstract
Angiotensin-converting enzyme 2 (ACE2) is a host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inhibiting the interaction between the envelope spike glycoproteins (S-proteins) of SARS-CoV-2 and ACE2 is a potential antiviral therapeutic approach, but little is known about how dietary compounds interact with ACE2. The objective of this study was to determine if flavonoids and other polyphenols with B-ring 3',4'-hydroxylation inhibit recombinant human (rh)ACE2 activity. rhACE2 activity was assessed with the fluorogenic substrate Mca-APK(Dnp). Polyphenols reduced rhACE2 activity by 15-66% at 10 μM. Rutin, quercetin-3-O-glucoside, tamarixetin, and 3,4-dihydroxyphenylacetic acid inhibited rhACE2 activity by 42-48%. Quercetin was the most potent rhACE2 inhibitor among the polyphenols tested, with an IC50 of 4.48 μM. Thus, quercetin, its metabolites, and polyphenols with 3',4'-hydroxylation inhibited rhACE2 activity at physiologically relevant concentrations in vitro.
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Affiliation(s)
- Xiaocao Liu
- College
of Food Science and Engineering, South China
University of Technology, Guangzhou 510640, China
- Department
of Food Science, University of Wisconsin-Madison, 1605 Linden Drive, Madison, Wisconsin 53706, United States
| | - Ruma Raghuvanshi
- Department
of Food Science, University of Wisconsin-Madison, 1605 Linden Drive, Madison, Wisconsin 53706, United States
| | - Fatma Duygu Ceylan
- Department
of Food Science, University of Wisconsin-Madison, 1605 Linden Drive, Madison, Wisconsin 53706, United States
- Faculty
of Chemical and Metallurgical Engineering, Department of Food Engineering, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey
| | - Bradley W. Bolling
- Department
of Food Science, University of Wisconsin-Madison, 1605 Linden Drive, Madison, Wisconsin 53706, United States
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35
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Hossain MF, Hasana S, Mamun AA, Uddin MS, Wahed MII, Sarker S, Behl T, Ullah I, Begum Y, Bulbul IJ, Amran MS, Rahman MH, Bin-Jumah MN, Alkahtani S, Mousa SA, Aleya L, Abdel-Daim MM. COVID-19 Outbreak: Pathogenesis, Current Therapies, and Potentials for Future Management. Front Pharmacol 2020; 11:563478. [PMID: 33178016 PMCID: PMC7596415 DOI: 10.3389/fphar.2020.563478] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 09/15/2020] [Indexed: 01/08/2023] Open
Abstract
At the end of 2019, a novel coronavirus (CoV) was found at the seafood market of Hubei province in Wuhan, China, and this virus was officially named coronavirus diseases 2019 (COVID-19) by World Health Organization (WHO). COVID-19 is mainly characterized by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) and creates public health concerns as well as significant threats to the economy around the world. Unfortunately, the pathogenesis of COVID-19 is unclear and there is no effective treatment of this newly life-threatening and devastating virus. Therefore, it is crucial to search for alternative methods that alleviate or inhibit the spread of COVID-19. In this review, we try to find out the etiology, epidemiology, symptoms as well as transmissions of this novel virus. We also summarize therapeutic interventions and suggest antiviral treatments, immune-enhancing candidates, general supplements, and CoV specific treatments that control replication and reproduction of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).
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Affiliation(s)
- Md. Farhad Hossain
- Department of Physical Therapy, Graduate School of Inje University, Gimhae, South Korea
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
| | - Sharifa Hasana
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
| | - Abdullah Al Mamun
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
| | - Md. Sahab Uddin
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
| | - Mir Imam Ibne Wahed
- Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh
| | - Sabarni Sarker
- Department of Pharmacy, Faculty of Life and Earth Sciences, Jagannath University, Dhaka, Bangladesh
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Irfan Ullah
- Kabir Medical College, Gandhara University, Peshawar, Pakistan
| | - Yesmin Begum
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
| | | | - Md. Shah Amran
- Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka, Bangladesh
| | - Md. Habibur Rahman
- Department of Global Medical Science, Yonsei University, Seoul, South Korea
| | - May N. Bin-Jumah
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Saad Alkahtani
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Shaker A. Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, New York, NY, United States
| | - Lotfi Aleya
- Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, Besançon, France
| | - Mohamed M. Abdel-Daim
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
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36
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Nicotianamine-rich foods for improving the learning and memory functions and as an effective preventing agent of hypertension. FOOD BIOSCI 2020. [DOI: 10.1016/j.fbio.2020.100729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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37
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Muchtaridi M, Fauzi M, Khairul Ikram NK, Mohd Gazzali A, Wahab HA. Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2. Molecules 2020; 25:E3980. [PMID: 32882868 PMCID: PMC7504743 DOI: 10.3390/molecules25173980] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/25/2020] [Accepted: 08/26/2020] [Indexed: 12/21/2022] Open
Abstract
Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.
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Affiliation(s)
- Muchtaridi Muchtaridi
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl Raya 21.5, Bandung-Sumedang 45363, Indonesia;
| | - M. Fauzi
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl Raya 21.5, Bandung-Sumedang 45363, Indonesia;
| | - Nur Kusaira Khairul Ikram
- Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia;
- Centre for Research in Biotechnology for Agriculture (CEBAR), Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Amirah Mohd Gazzali
- Department of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia;
| | - Habibah A. Wahab
- Pharmaceutical Design and Simulation Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia
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38
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Khodadadi E, Maroufi P, Khodadadi E, Esposito I, Ganbarov K, Espsoito S, Yousefi M, Zeinalzadeh E, Kafil HS. Study of combining virtual screening and antiviral treatments of the Sars-CoV-2 (Covid-19). Microb Pathog 2020; 146:104241. [PMID: 32387389 PMCID: PMC7199731 DOI: 10.1016/j.micpath.2020.104241] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 04/28/2020] [Accepted: 04/29/2020] [Indexed: 02/07/2023]
Abstract
The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Additionally, general treatments, coronavirus-specific treatments, and antiviral treatments useful in fighting COVID-19 are addressed. This review sets out to shed light on the SARS-CoV-2 and host receptor recognition, a crucial factor for successful virus infection and taking immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein of SARS-CoV-2. A variety of improved or new approaches also have been developed. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection. Moreover, the genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three-dimensional structure of the Main protease (Mpro) is available. The reported structure of the target Mpro was described in this review to identify potential drugs for COVID-19 using virtual high throughput screening.
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Affiliation(s)
- Ehsaneh Khodadadi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Parham Maroufi
- Department of Orthopedy, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Ehsan Khodadadi
- Department of Biology, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
| | | | | | | | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Elham Zeinalzadeh
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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39
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Zamai L. The Yin and Yang of ACE/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients. Cells 2020; 9:E1704. [PMID: 32708755 PMCID: PMC7408073 DOI: 10.3390/cells9071704] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 06/10/2020] [Accepted: 06/25/2020] [Indexed: 02/06/2023] Open
Abstract
The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms. Based purely on experimental studies in which RAS pathway inhibitors were administered in vivo to humans/rodents, a reasonable hypothesis of using inhibitors that block both ACE and ACE2 zinc metalloproteases and their downstream pathways in COVID-19 patients will be proposed. In particular, metal (zinc) chelators and renin inhibitors may work alone or in combination to inhibit the positive feedback loops (initially triggered by SARS-CoV-2 and subsequently sustained by hypoxia independently on viral trigger) as both arms of renin-angiotensin system are upregulated, leading to critical, advanced and untreatable stages of the disease.
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Affiliation(s)
- Loris Zamai
- Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, 61032 Urbino, Italy; ; Tel.: +39-0722-304319
- INFN-Gran Sasso National Laboratory, Assergi, 67100 L’Aquila, Italy
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40
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Zhou J, Huang J. Current Findings Regarding Natural Components With Potential Anti-2019-nCoV Activity. Front Cell Dev Biol 2020; 8:589. [PMID: 32719799 PMCID: PMC7351523 DOI: 10.3389/fcell.2020.00589] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 06/17/2020] [Indexed: 12/19/2022] Open
Abstract
COVID-19, a novel coronavirus pneumonia (named by the World Health Organization, WHO), has spread widely since the end of 2019. Research on synthetic drugs and vaccines has become a focus of attention in China and other countries, as such approaches are regarded as key tools for disease prevention and control; however, the development of these therapeutics will take months, or even years. Under such circumstances, development of coronavirus specific therapeutics is urgent. For this specific indication, the rapid performance of natural products, such as plant compounds, herbal extracts, and traditional Chinese medicine, could contribute as alternative measures. Recent investigations have provided evidence that these natural products are potential candidates for development as therapeutic agents against the virus that causes COVID-19, 2019-nCoV. Targeting the structural proteins or cellular receptors of 2019-nCoV, including coronavirus chymotrypsin-like (3CLpro or Mpro), helicase (nsP13), S protein, and human angiotensin converting enzyme 2 (ACE2), holds promise for preventing infection. In this review, we summarize some representative natural products and their active components that have potential anti-2019-nCoV effects. We focus on the basic structural elements of 2019-nCoV, its main mechanisms of action, and the feasibility and potential of products to inhibit the novel coronavirus. In addition, the relative advantages, additional functions, and precautions that should be used with typical natural products are also discussed. The aim is to make the case that natural products could be a valuable pool for the development of active compounds for treating 2019-nCoV infection, which may contribute to mitigation of the spread of the pandemic.
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Affiliation(s)
- Jin Zhou
- Shenzhen International Graduate School, Tsinghua University, Shenzhen, China
| | - Jie Huang
- Network of Aquaculture Centres in Asia-Pacific, Bangkok, Thailand
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Yellow Sea Fisheries Research Institute, Qingdao, China
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41
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McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res 2020; 157:104859. [PMID: 32360480 PMCID: PMC7189851 DOI: 10.1016/j.phrs.2020.104859] [Citation(s) in RCA: 347] [Impact Index Per Article: 69.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 04/20/2020] [Accepted: 04/22/2020] [Indexed: 12/20/2022]
Abstract
Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.
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Affiliation(s)
| | - Ariane Sternberg
- Center and Network for Targeted Oncology, Muehlackerweg 8, D-69239, Heidelberg, Germany
| | - Ulrike Stange
- Center and Network for Targeted Oncology, Muehlackerweg 8, D-69239, Heidelberg, Germany
| | - Stefan Laufer
- Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität, Tübingen and Tuebingen Center for Academic Drug Discovery, Auf Der Morgenstelle 8, 72076, Tuebingen, Germany
| | - Cord Naujokat
- Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-69120, Heidelberg, Germany.
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42
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Abstract
COVID-19 has been the most devastating pandemic in human history. Despite the highest scientific efforts and investments, a reliable and certified medication has yet to be developed regarding to immune or cure this virus. However, while synthetic medications are gaining the focus of attentions, it appears from a significant number of recent studies that plant-based substances could also be potential candidates for developing effective and secure remedies against this novel disease. Citing such recent works, this review primarily demonstrates the antiviral potentials of medicinal plants for inhibiting human coronaviruses. It also shows the importance of antiviral plants substances, particularly in the development of a broad spectrum medication for coronaviruses including SARS-CoV-2 responsible for COVID-19.
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Affiliation(s)
- Israt Jahan
- Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yıldız Technical University, İstanbul Turkey
| | - Ahmet Onay
- Department of Biology, Faculty of Science, Dicle University, Diyarbakır Turkey
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43
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Hamed MA. An overview on COVID-19: reality and expectation. BULLETIN OF THE NATIONAL RESEARCH CENTRE 2020; 44:86. [PMID: 32514228 PMCID: PMC7266424 DOI: 10.1186/s42269-020-00341-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 05/20/2020] [Indexed: 05/08/2023]
Abstract
Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. By the declaration of WHO, COVID-19 outbreak considered as a public health problem of international concern. The aim of this study is to provide a comprehensive view on COVID-19 and the future expectations to control virus progression. Patients with liver disease, diabetes, high blood pressure, and obesity are more susceptible to the incidence of COVID-19 infection. So, there is a rapid need for disease diagnosis, vaccine development, and drug discovery to detect, prevent, and treat this sudden and lethal virus. Real-time polymerase chain reaction (RT-PCR) is considered as a rapid, accurate, and specific tool for disease diagnosis. Under this emergency situation that the world facing against COVID-19, there are about 15 potential vaccine candidates tested globally based on messenger RNA, DNA-based, nanoparticle, synthetic, and modified virus-like particle. Certain drugs that are clinically approved for other diseases were tested against COVID-19 as chloroquine, hydroxychloroquine, ivermectin, favipiravir, ribavirin, and remdesivir. Convalescent plasma transfusion and traditional herbal medicine were also taken into consideration. Due to the absence of effective treatment or vaccines against COVID-19 so far, the precautionary measures according to WHO's strategic objectives are the only way to confront this crisis. Governments should adopt national medical care programs to reduce the risk of exposure to any future viral outbreaks especially to patients with pre-existing medical conditions.
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Affiliation(s)
- Manal A. Hamed
- Department of Therapeutic Chemistry, National Research Centre, El-Buhouth St., Dokki, Giza, Egypt
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44
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Barabari P, Moharamzadeh K. Novel Coronavirus (COVID-19) and Dentistry-A Comprehensive Review of Literature. Dent J (Basel) 2020; 8:E53. [PMID: 32455612 PMCID: PMC7345990 DOI: 10.3390/dj8020053] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 05/15/2020] [Accepted: 05/19/2020] [Indexed: 01/08/2023] Open
Abstract
The novel coronavirus (COVID-19) pandemic has become a real challenge for healthcare providers around the world and has significantly affected the dental professionals in practices, universities and research institutions. The aim of this article was to review the available literature on the relevant aspects of dentistry in relation to COVID-19 and to discuss potential impacts of COVID-19 outbreak on clinical dentistry, dental education and research. Although the coronavirus pandemic has caused many difficulties for provision of clinical dentistry, there would be an opportunity for the dental educators to modernize their teaching approaches using novel digital concepts in teaching of clinical skills and by enhancement of online communication and learning platforms. This pandemic has also highlighted some of the major gaps in dental research and the need for new relevant knowledge to manage the current crisis and minimize the impact of such outbreaks on dentistry in the future. In conclusion, COVID-19 has had many immediate complications for dentistry of which some may have further long-term impacts on clinical practice, dental education and dental research.
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Affiliation(s)
- Poyan Barabari
- Eastman Dental Institute, University College London, London WC1X 8WD, UK;
| | - Keyvan Moharamzadeh
- School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK
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45
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Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. Int J Biol Sci 2020; 16:1708-1717. [PMID: 32226288 PMCID: PMC7098036 DOI: 10.7150/ijbs.45538] [Citation(s) in RCA: 558] [Impact Index Per Article: 111.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 03/08/2020] [Indexed: 02/07/2023] Open
Abstract
Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.
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Affiliation(s)
| | | | | | | | - Xin Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
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46
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Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol 2020; 92:479-490. [PMID: 32052466 PMCID: PMC7166986 DOI: 10.1002/jmv.25707] [Citation(s) in RCA: 721] [Impact Index Per Article: 144.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 02/04/2020] [Indexed: 12/14/2022]
Abstract
An outbreak of a novel coronavirus (COVID‐19 or 2019‐CoV) infection has posed significant threats to international health and the economy. In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of disease. Here, we have conducted an online search for all treatment options related to coronavirus infections as well as some RNA‐virus infection and we have found that general treatments, coronavirus‐specific treatments, and antiviral treatments should be useful in fighting COVID‐19. We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children's RNA‐virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, convalescent plasma should be given to COVID‐19 patients if it is available. In conclusion, we suggest that all the potential interventions be implemented to control the emerging COVID‐19 if the infection is uncontrollable.
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Affiliation(s)
- Lei Zhang
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yunhui Liu
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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47
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Minato T, Nirasawa S, Sato T, Yamaguchi T, Hoshizaki M, Inagaki T, Nakahara K, Yoshihashi T, Ozawa R, Yokota S, Natsui M, Koyota S, Yoshiya T, Yoshizawa-Kumagaye K, Motoyama S, Gotoh T, Nakaoka Y, Penninger JM, Watanabe H, Imai Y, Takahashi S, Kuba K. B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction. Nat Commun 2020; 11:1058. [PMID: 32103002 PMCID: PMC7044196 DOI: 10.1038/s41467-020-14867-z] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 02/10/2020] [Indexed: 12/12/2022] Open
Abstract
Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1–7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Our data identify the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure. The enzyme ACE2 is involved in cardiac pathology and can counteract heart failure and other cardio-pulmonary diseases. Here the authors show that bacteria produce an ACE2-like enzyme that is effective in suppressing cardiac hypertrophy and fibrosis in mice.
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Affiliation(s)
- Takafumi Minato
- Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Satoru Nirasawa
- Biological Resources and Post-harvest Division, Japan International Research Center for Agricultural Sciences, 1-1 Ohwashi, Tsukuba, Ibaraki, 305-8686, Japan.
| | - Teruki Sato
- Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.,Department of Cardiovascular Medicine, Akita University Graduate School of Medicine, Akita, Japan
| | - Tomokazu Yamaguchi
- Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Midori Hoshizaki
- Laboratory of Regulation of Intractable Infectious Diseases, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan
| | - Tadakatsu Inagaki
- Department of Vascular Physiology, Research Institute National Cerebral and Cardiovascular Center, 6-1 Kishibe Shinmachi, Suita, Osaka, 564-8565, Japan
| | - Kazuhiko Nakahara
- Biological Resources and Post-harvest Division, Japan International Research Center for Agricultural Sciences, 1-1 Ohwashi, Tsukuba, Ibaraki, 305-8686, Japan
| | - Tadashi Yoshihashi
- Biological Resources and Post-harvest Division, Japan International Research Center for Agricultural Sciences, 1-1 Ohwashi, Tsukuba, Ibaraki, 305-8686, Japan
| | - Ryo Ozawa
- Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Saki Yokota
- Department of Materials Science, Applied Chemistry Course, Graduate School of Engineering Science, Akita University, 1-1 Tegatagakuen-machi, Akita, 010-8502, Japan
| | - Miyuki Natsui
- Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Souichi Koyota
- Molecular Medicine Laboratory, Bioscience Education and Research Support Center, Akita University, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Taku Yoshiya
- Peptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan
| | | | - Satoru Motoyama
- Department of Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Takeshi Gotoh
- Department of Materials Science, Applied Chemistry Course, Graduate School of Engineering Science, Akita University, 1-1 Tegatagakuen-machi, Akita, 010-8502, Japan
| | - Yoshikazu Nakaoka
- Department of Vascular Physiology, Research Institute National Cerebral and Cardiovascular Center, 6-1 Kishibe Shinmachi, Suita, Osaka, 564-8565, Japan
| | - Josef M Penninger
- IMBA -Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Campus Vienna BioCenter, Vienna, 1030, Austria.,Department of Medical Genetics, Life Science Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada
| | - Hiroyuki Watanabe
- Department of Cardiovascular Medicine, Akita University Graduate School of Medicine, Akita, Japan
| | - Yumiko Imai
- Laboratory of Regulation of Intractable Infectious Diseases, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan
| | - Saori Takahashi
- Akita Research Institute of Food and Brewing, 4-26 Sanuki, Arayamachi, Akita, 010-1623, Japan
| | - Keiji Kuba
- Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
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Sistema renina-angiotensina-aldosterona y COVID19. Implicaciones clínicas. REVISTA ESPAÑOLA DE CARDIOLOGÍA SUPLEMENTOS 2020. [PMCID: PMC7668217 DOI: 10.1016/s1131-3587(20)30032-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
La pandemia ocasionada por la rápida expansión del SARS-CoV-2 ha producido la mayor crisis sanitaria de la época moderna. La estrecha relación del virus con la enzima de conversión de la angiotensina ha suscitado un torrente de especulaciones por el posible papel del sistema renina-angiotensina-aldosterona (SRAA) en la regulación de la infección. La alerta generada ha cuestionado el empleo de fármacos inhibidores del SRAA, tanto los inhibidores de la enzima de conversión de la angiotensina como los antagonistas del receptor de la angiotensina II. Esta situación ha motivado la publicación de varios estudios que no han encontrado asociación entre el uso de inhibidores del SRAA y una mayor susceptibilidad a la infección o a una peor evolución clínica. En esta revisión se abordan los aspectos más relevantes de la interacción del SARS-CoV-2 con el SRAA y las implicaciones clínicas en torno al uso de inhibidores del SRAA durante la pandemia.
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