Remdesivir for COVID-19: A review of pharmacology, mechanism of action, in-vitro activity and clinical use based on available case studies
Abstract
Remdesivir as a drug attracted a very serious consideration of whole Globe in treatment of the pandemic disease COVID-19. More recently published in-vitro inhibition activity and in-vivo case studies were showing promising clinical results and outcome of effective inhibition of SARS-CoV-2 virus by the use of remdesivir. However at the same time, use of the remdesivir showed substantial detrimental adverse events in patients which needs a special attention during treatment course of COVID-19. Thus, the use of remdesivir in treatment of COVID-19 is having current international interest although some more clinical evidences are still necessary in order to understand the actual efficiency and mechanism of remdesivir against COVID-19. In view of this, the present literature study spotlight the current ongoing research related to use of remdesivir which includes (i) pharmacology of remdesivir, (ii) mechanism of action of remdesivir (iii) in-vitro inhibition of remdesivir against SARS-CoV-2 virus, (iv) in-vivo analysis and clinical use of remdesivir against COVID-19. Finally possible adverse events (of use of remdesivir) are also discussed considering the pharmacovigilance concern.
Keywords: Remdesivir; COVID-19; Remdesivir side effects, Remdesivir pharmacology; SARS-CoV-2 virus
Keywords:
Remdesivir, COVID-19, Remdesivir side effects, Remdesivir pharmacology, SARS-CoV-2 virusDOI
https://doi.org/10.22270/jddt.v10i4-s.4313References
Badgujar KC, Badgujar AB, Patil VP, Dhangar DV. Hydroxychloroquine for COVID-19: A review and a debate based on available clinical trials/case studies. JDDT [Internet]. 15May2020 [cited 13Jul.2020];10(3):304-11. Available from: http://jddtonline.info/index.php/jddt/article/view/4110
Badgujar KC, Patil DV, Dhangar DV, Patil VP, Badgujar AB.COVID-19: Epidemiology, clinical characteristics and potential possible treatment based on available studies, Revision submitted manuscript, Coronaviruses Journal, Bentham Science Publication
Badgujar KC, Badgujar VC, Badgujar SB, Coronavirus vaccine development (2003 to present): an overview, recent advances, current scenario, opportunities and challenges. diabetes and metabolic syndrome clinical research and reviews, Revision submitted manuscript, Elsevier Publication
https://www.worldometers.info/coronavirus/
Singh A, Shaikh A, Singh R, Singh AK. COVID-19: From bench to bed side [published online ahead of print, 2020 Apr 9]. Diabetes Metab Syndr. 2020;14(4):277-281. doi:10.1016/j.dsx.2020.04.011
https://www.fda.gov/media/137564/download
Singh AK, Singh A, Singh R, Misra A. Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies [published online ahead of print, 2020 May 12]. Diabetes Metab Syndr. 2020;14(4):641-648. doi:10.1016/j.dsx.2020.05.018
https://www.nytimes.com/2020/04/17/opinion/remdesivir-coronavirus.html
Stephens B (18 April 2020). "The Story of Remdesivir". The New York Times. p. A23
Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):222. Published 2020 Jan 10. doi:10.1038/s41467-019-13940-6
de Wit E, Feldmann F, Cronin J, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2020;117(12):6771-6776. doi:10.1073/pnas.1922083117
Agostini ML, Andres EL, Sims AC, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio. 2018;9(2) doi: 10.1128/mBio.00221-18.
Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396) doi: 10.1126/scitranslmed.aal3653.
Brown AJ, Won JJ, Graham RL, Dinnon KH 3rd, Sims AC, Feng JY, Cihlar T, Denison MR, Baric RS, Sheahan TP. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019 Sep; 169():104541.
Gudipati, Pavan; Biswas, Shyamasri; goyal, pankaj (2020): Anti Hepatitis C Viral Drugs Remdesivir and Uprifosbuvir Derivatives Are Better Inhibitors of SARS Cov2 RNA-Dependent RNA Polymerase Determined by Docking Studies. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12443237.v2
Lo MK, Feldmann F, Gary JM, et al. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci Transl Med. 2019;11(494):eaau9242. doi:10.1126/scitranslmed.aau9242
Porter DP et al., Remdesivir (GS-5734) Is Efficacious in Cynomolgus Macaques Infected With Marburg Virus, The Journal of Infectious Diseases, , jiaa290, https://doi.org/10.1093/infdis/jiaa290
Ye W, Yao M, Dong Y, et al. Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition. Front Microbiol. 2020;11:1105. Published 2020 Jun 12. doi:10.3389/fmicb.2020.01105
Lo MK, Jordan R, Arvey A, et al. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci Rep. 2017;7:43395. Published 2017 Mar 6. doi:10.1038/srep43395
Tchesnokov EP, Feng JY, Porter DP, Götte M. Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir. Viruses. 2019;11(4):326. Published 2019 Apr 4. doi:10.3390/v11040326
Warren TK et al., Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016 Mar 17;531(7594):381-5. doi: 10.1038/nature17180. Epub 2016 Mar 2. (PubMed ID 26934220)
https://www.drugbank.ca/drugs/DB01611#reference-L8072
Furst DE: Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus. 1996 Jun;5 Suppl 1:S11-5. (PubMed ID 8803904)
https://www.fda.gov/media/137566/download
https://www.drugbank.ca/drugs/DB14761#reference-L13239
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf
Furst DE: Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus. 1996 Jun;5 Suppl 1:S11-5. (PubMed ID 8803904)
https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf
Vander T, Medvedovsky M, Herishanu Y: Encephalopathy induced by oral acyclovir in a patient with normal renal function. J Infect. 2003 May;46(4):286. doi: 10.1053/jinf.2002.1119
Tchesnokov EP, Feng JY, Porter DP, Götte M. Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir. Viruses. 2019;11(4):326. Published 2019 Apr 4. doi:10.3390/v11040326.
Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, Hall MD (May 2020). "Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19". ACS Cent. Sci. 6 (5): 672–683. doi:10.1021/acscentsci.0c00489. PMC 7202249. PMID 32483554
Al-Tannak NF, Novotny L, Alhunayan A, Remdesivir-Bringing Hope for COVID-19 Treatment Sci. Pharm. 2020, 88(2), 29; https://doi.org/10.3390/scipharm88020029 DOI: https://doi.org/10.3390/scipharm88020029
Saha A, Sharma AR, Bhattacharya M, Sharma G, Lee SS, Chakraborty C. Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More [published online ahead of print, 2020 May 12]. Arch Med Res. 2020;S0188-4409(20)30699-8. doi:10.1016/j.arcmed.2020.05.001
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-637. doi:10.1002/path.1570
Gu J, Han B, Wang J (May 2020). "COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission". Gastroenterology. 158 (6): 1518–1519. doi:10.1053/j.gastro.2020.02.054
Chai XQ, Hu LF, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after COVID-19 infection. Preprint. Posted online February 03, 2020. bioRxiv 931766. DOI: https://doi.org/10.1101/2020.02.03.931766
Fan C, Li K, Ding Y, Lu WL, Wang J. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. MedRxiv. 2020 Jan 1.
https://www.clinicaltrialsarena.com/projects/remdesivir/
European Medicines Agency: https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf
Choy KT, Wong AY, Kaewpreedee P, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020;178:104786. doi:10.1016/j.antiviral.2020.104786
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. doi:10.1038/s41422-020-0282-0
Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396):eaal3653. doi:10.1126/scitranslmed.aal3653
Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019;169:104541. doi:10.1016/j.antiviral.2019.104541
Pruijssers AJ, Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. bioRxiv preprint doi: https://doi.org/10.1101/2020.04.27.064279
Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Lancet. 2020. Lancet. 2020;395(10236):1569-1578. doi:10.1016/S0140-6736(20)31022-9
Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020;382(24):2327-2336. doi:10.1056/NEJMoa2007016.
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report. N Engl J Med. 2020;NEJMoa2007764. doi:10.1056/NEJMoa2007764.
Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020;10.1056/NEJMoa2015301. doi:10.1056/NEJMoa2015301.
Hillaker E, Belfer JJ, Bondici A, Murad H, Dumkow LE. Delayed Initiation of Remdesivir in a COVID-19 Positive Patient. Pharmacotherapy 2020
Kujawski S, Wong KK, Collins JP. First 12 patients with coronavirus disease 2019 (COVID-19) in the United Staes. https://doi org/10 1101/2020 03 09 20032896 2020
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