Remdesivir-A Possible Therapeutic Measure to Stem the Pandemic Wave
By: Umer Farooq, Aroosh Shabbir, Arsalan Fazal, Maryam Khan, Saba Shamim
Key Words: Coronaviruses, COVID-19, Remdesivir, MERS-CoV, SARS-CoV-2, FDA.
Int. J. Biosci. 18(3), 59-73, March 2021.
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The year 2020 will always be recalled in human history as the year of the COVID-19 pandemic. Its crisis at the global level has united scientists all over the world for the development of potential therapeutic drugs for its treatment. Remdesivir remains in limelight owing to its efficacy. The initial clinical trials showed a better benefit-ratio profile ratio. However, its safety is not established yet. The drug is under investigation. The ongoing clinical trials have proposed a better benefit-risk profile of remdesivir as compared to the placebo. Both in vitro and in vivo, remdesivir is one of the potential drugs which has demonstrated its efficacy against the Coronaviruses. It has also shown its promising support as a compassionate use drug for the clinical improvement of patients in the COVID-19 challenge. It is expected from the clinical trials progress that remdesivir will show the outstanding breakthroughs for the global COVID-19 challenge. Moreover, FDA approval has created a hope that the use of remdesivir may be helpful in the mitigation of morbidity, mortality, and the burden on the health care systems due to COVID-19 in the future.
Remdesivir-A Possible Therapeutic Measure to Stem the Pandemic Wave
Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR. 2018. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio 9(2), 1-15.
Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, Wit Ed, Munster VJ, Hensley LE, Zalmout IS, Kapoor A, Epstein JH, Karesh WB, Daszak P, Mohammad OB, Lipkin WI. 2014. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. mBio 5(2), 1-7.
Allison M. 2012. NCATS launches drug repurposing program. Nature Biotechnology 30(7), 571-572.
Al-Tawafiq JA, Al-Homoud AH, Memish ZA. 2020. Remdesivir as a possible therapeutic option for the COVID-19. Travel Medicine and Infectious Disease 34, 1-2.
Amanat F, Krammer F. 2020. SARS-CoV-2 Vaccines: Status Report. Immunity 52(4), 583-589.
Amiriana ES, Levy JK. 2020. Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses. One Health 9, 1-21.
Baden LR, Rubin EJ. 2020. Covid-19 – the search for effective therapy. The New England Journal of Medicine 382(19), 1851-1852.
Bawazir A, Al-Mazroo E, Jradi H, Ahmed A, Badri M. 2018. MERS-CoV infection: mind the public knowledge gap. Journal of Infection and Public Health 11(1), 89-93.
Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T. 2020. Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper. JHEP Reports 2(3), 1-8.
Brown AJ, Won JJ, Graham RL, Dinnon 3rd KH, Sims AC, Feng JY, Cihlar T, Denison MR, Bric RS, Sheahan TP. 2019. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Research 169, 1-11.
Cao YC, Deng QX, Dai SX. 2020a. Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence. Travel Medicine and Infectious Disease 35, 1-7.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. 2020b. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. The New England Journal of Medicine 382, 1787-1799.
CDC. 2014-2016. Ebola outbreak in West Africa. (Website accessed on March 12, 2019. www.cdc.gov/vhf/ebola/history/2014-2016-outbreak/index.html)
Chen WH, Strych U, Hotez PJ, Bottazzi ME. 2020a. The SARS-CoV-2 vaccine pipeline: an overview. Current Tropical Medicine Reports 7, 61-64.
Chen Y, Liu Q, Guo D. 2020b. Emerging coronaviruses: genome structure, replication, and pathogenesis. Journal of Medical Virology 92(4), 418-423.
Chen C, Zhang Y, Huang J, Yin P, Cheng Z, Wu J, Chen S, Zhang Y, Chen B, Lu M, Luo Y, Ju L, Zhang J, Wang X. 2020c. Favipiravir versus Arbidol for Covid-19: a randomized clinical trial. medRxiv.
Choy KT, Wonga AYL, Kaewpreedeea P, Sin SF, Chen D, Hui KPY, Chu DKW, Chan MCW, Cheung PPH, Huang X, Peiris M, Yen HL. 2020. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Research 178, 1-5.
Clinical Trials. 2020. A trial of remdesivir in adults with mild and moderate COVID-19. (Webpage accessed on April 15, 2020 at
Cui J, Li F, Shi ZL. 2019. Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology 17, 181-192.
Davies M, Osborne V, Lane S, Roy D, Dhanda S, Evans A, Shakir S. 2020. Remdesivir in treatment of COVID-19: A systematic benefit-risk assessment. Drug Safety 43(7), 645-656.
Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, Hall MD. 2020. Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS Central Science 6(5), 672-683.
Fearns R, Plemper RK. 2017. Polymerases of paramyxoviruses and pneumoviruses. Virus Research 234, 87-102.
Fine P, Eames K, Heymann DL. 2011. “Herd immunity”: a rough guide. Clinical Infectious Diseases 52(7), 911-916.
Food and Drug Administration. 2020. FDA approves first treatment for COVID-19. U.S (Press release). (Webpage accessed on October 22, 2020 at https://www.fda.gov/news-events/pressannouncements/fda-approves-first-treatment-covid-19)
Furuta Y, Komeno T, Nakamura T. 2017. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proceedings of the Japan Academy, Series B, Physical and Biological Sciences 93(7), 449-463.
Gao J, Tian Z, Yang X. 2020. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Bioscience Trends 14(1), 72-73.
Gilead. 2020. Gilead announces results from phase 3 trial of investigational antiviral remdesivir in patients with severe COVID-19. (Website accessed on April 24, 2020 at
Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Götte M. 2020. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. The Journal of Biological Chemistry 295(15), 4773-4779.
Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A. 2020. Compassionate use of remdesivir for patients with Severe Covid-19. The New England Journal of Medicine 382, 2327-2336.
Grollman AP. 1966. Structural basis for inhibition of protein synthesis by emetine and cycloheximide based on an analogy between ipecac alkaloids and glutarimide antibiotics. Proceedings of the National Academy of Sciences of the United States of America 56(6), 1867-1874.
Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL. 2003. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302(5643), 276-278.
Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A. 2015. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. The Lancet 386(9996), 857-866.
Hodgson J. 2020. The pandemic pipeline. Nature Biotechnology 38, 523-532.
Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H. 2020. First case of 2019 novel coronavirus in the United States. The New England Journal of Medicine 382, 929-936.
Hui DS, Azhar IE, Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E. 2020. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – the latest 2019 novel coronavirus outbreak in Wuhan, China. International Journal of Infectious Diseases 91, 264-266.
Ianevski A, He L, Aittokallio T, Tang J. 2017. SynergyFinder: a web application for analyzing drug combination dose-response matrix data. Bioinformatics 33(15), 2413–2415.
Jacobs M, Rodger A, Bell DJ, Bhagani S, Cropley I, Filipe A. 2016. Late Ebola virus relapse causing meningoencephalitis: a case report. The Lancet 388(10043), 498-503.
Jean SS, Lee PI, Hsueh PR. 2020. Treatment options for COVID-19: The reality and challenges. Journal of Microbiology, Immunology and Infection 53(3), 436-443.
Ji W, Wang W, Zhao X, Zai J, Li X. 2020. Cross-species transmission of the newly identified coronavirus 2019-nCoV. Journal of Medical Virology 92(4), 433-440.
Jordan PC, Liu C, Raynaud P, Lo MK, Spiropoulou CF, Symons JA, Beigelman L, Deval J. 2018. Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase. PLoS Pathogens 14(2), 1-23.
Khan S, Nabi G, Han G, Siddique R, Lian S, Shi H, Bashir N, Ali A, Shereen MA. 2020a. Novel coronavirus: how the things are in Wuhan. Clinical Microbiology and Infection 26(4), 399-400.
Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q, Bashir N, Xue M. 2020b. Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: biology and therapeutic options. Journal of Clinical Microbiology 58(5), 1-11.
Kim JY, Choe PG, Oh Y Oh KJ, Kim J, Park SJ, Park JH, Na HK, Oh MD. 2020. The first case of 2019 novel coronavirus pneumonia imported into Korea from Wuhan, China: implication for infection prevention and control measures. Journal of Korean Medical Science 35(5), 1-4.
Kirchdoerfer RN. 2020. Halting coronavirus polymerase. Journal of Biological Chemistry 295(15), 4780-4781.
Ko WC, Rolain JM, Lee NY, Chen PL, Huang CT, Lee PI, Hsueu PR. 2020. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. International Journal of Antimicrobial Agents 55(4), 1-3.
Kouznetsova, J, Sun W, Martínez-Romero C, Tawa G, Shinn P, Chen CZ, Schimmer A, Sanderson P, McKew JC, Zheng W, García-Sastre A. 2014. Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs. Emerging Microbes and Infections 3(12), 1-7.
Kumar S, Haqqani H, Wynn G, Pathak RK, Lipton J, Mahajan R. 2020. Position statement on the management of cardiac electrophysiology and cardiac implantable electronic devices in Australia during the COVID-19 pandemic: A living document. Heart, Lung and Circulation 29(6), e57-e68.
Lamb YN. 2020. Remdesivir: First approval. Drugs 80, 1355-1363.
Lo MK, Feldmann F, Gary JM, Jordon R, Bannister R, Cronin J, Patel NR, Klena JD, Nichol ST, Cihlar T, Zaki SR, Feldmann H, Spiropoulou CF, Wit E. 2019. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Science Translational Medicine 11(494), 1-12.
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y. 2020. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. The New England Journal of Medicine 382, 1199-1207.
Lo MK, Jordan R, Arvey A, Sudhamsu J, Shrivastava-Ranjan P, Hotard AL. 2017. GS-5734 and its parent nucleoside analog inhibit filo-, pneumo-, and paramyxoviruses. Scientific Reports 7(6), 43395-43401.
Long B, Brady WJ, Koyfman A, Gottlieb M. 2020. Cardiovascular complications in COVID-19. The American Journal of Emergency Medicine 38(7), 1504-1507. https://dx.doi.org/10.1016/j.ajem.2020.04.048
Mahase E. 2020. Covid-19: what treatments are being investigated? The BMJ 368, 1-2.
Morse JS, Lalonde T, Xu S, Liu WR. 2020. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. Chembiochem 21(5), 730-738.
Mühlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. 1999. Comparison of the transcription and replication strategies of Marburg virus and Ebola virus by using artificial replication systems. Journal of Virology 73(3), 2333-2342. https://dx.doi.org/10.1128/JVI.73.3.2333-2342.1999.
Mulangu S, Dodd LE, Davey RT, Mbaya OT, Proschan M, Mukadi D. 2019. A randomized, controlled trial of Ebola virus disease therapeutics. The New England Journal of Medicine 381, 2293-2303.
Norrie JD. 2020. Remdesivir for COVID-19: challenges of underpowered studies. The Lancet 395(10236), 1525-1527.
Oestereich L, Lüdtke A, Wurr S, Rieger T, Muňoz-Fontela C, Günther S. 2014. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Research 105, 17-21.
Onder G, Rezza G, Brusaferro S. 2020. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. The Journal of the American Medical Association 323(18), 1775-1776.
Paules CI, Marston HD, Fauci AS. 2020. Coronavirus infections – more than just the common cold. The Journal of the American Medical Association 323(8), 707-708.
Philippidis A. 2020. Catching up to coronavirus: top 60 treatments in development. Genetic Engineering & Biotechnology News. Website accessed on April 10, 2020 at https://www.genengnews.com/virology/coronavirus/catching-up-to-coronavirus-top-60-treatments-in-development/)
Poston JT, Patel BK, Davis AM. 2020. Management of critically ill adults with COVID-19. The Journal of the American Medical Association 323(18), 1839-1841.
Scavone C, Brusco S, Bertini M, Sportiello L, Rafaniello C, Zoccoli A. 2020. Current pharmacological treatments for COVID-19: what’s next? British Journal of Pharmacology 177(21), 4813-4824.
Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB. 2017. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Science Translational Medicine 9(396), 1-20.
Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ. 2020. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nature Communications 11, 222-235.
Shen C, Wang Z, Zhao F. 2020. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. The Journal of the American Medical Association 323(16), 1582-1589.
Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L. 2017. Discovery and synthesis of a phosphoramidate prodrug of a Pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses. Journal of Medical Chemistry 60(5), 1648-1661.
Singh AK, Singh R, Saboo B, Misra A. 2021. Non-insulin anti-diabetic agents in patients with type 2 diabetes ad COVID-19: a critical appraisal of literature. Diabetes and Metabolic Syndrome: Clinical Research and Reviews 15(1), 159-167.
Smither SJ, Eastaugh LS, Steward JA, Nelson M, Lenk RP, Lever MS. 2014. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Research 104, 153-155.
Tchesnokov EP, Raeisimakiani P, Ngure M, Marchant D, Götte M. 2018. Recombinant RNA-dependent RNA polymerase complex of Ebola virus. Scientific Reports 8, 1-9.
Tchesnokov EP, Feng JY, Porter DP, Götte M. 2019. Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses 11(4), 326-342.
Touret F, de Lamballerie X. 2020. Of chloroquine and COVID-19. Antiviral Research 177, 1-3. https://dx.doi.org/10.1016/j.antiviral.2020.104762
US Food and Drug Administration. 2020. Fact sheet for health care providers: emergency use authorization (EUA) of Veklury (remdesivir). Revised 08/2020. US Food and Drug Administration, Silver Spring, MD, Avaiable from:
US National Library of Medicine Clinical Trials Registry. 2020. Study to evaluate the safety and antiviral activity of remdesivir (GS-5734™) in participants with severe coronavirus disease (COVID-19), Available from: show/NCT04292899 (accessed on 13 March 2020).
Vabret A, Dina J, Mourez T, Gouarin S, Petitjean J, van der Werf S, Freymuth F. 2006. Inter- and intra-variant genetic heterogeneity of human coronavirus OC43 strains in France. The Journal of General Virology 87(11), 3349-3353.
Vassilara F, Spyridaki A, Pothitos G, Deliveliotou A, Papadopoulos A. 2018. A rare case of human coronavirus 229E associated with acute respiratory distress syndrome in a healthy adult. Case Reports in Infectious Diseases 2018, 1-5.
Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y. 2020a. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet 395(10236), 1569-1578.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. 2020b. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV)
in vitro. Cell Research 30, 269-271.
Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL, Tongeren SAV. 2014. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 508(7096), 402-405.
Warren T, Jordan R, Lo M, Soloveva V, Ray A, Bannister R. 2015. Nucleotide prodrug GS-5734 is a broad-spectrum filovirus inhibitor that provides complete therapeutic protection against the development of Ebola virus disease (EVD) in infected non-human primates. Open Forum Infectious Diseases 2(1), S67.
Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V. 2016. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 531, 381-385.
Wong W, Bai XC, Brown A, Fernandez IS, Hanssen E, Condron M, Tan YH, Baum J, Scheres SHW. 2014. Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. eLife 3, 1-4.
World Health Organization. 2016. Ebola situation report. (Website accessed on March 19, 2020 at
World Health Organization. 2019. List of blueprint priority diseases. (Website accessed on March 12, 2019 at
World Health Organization. 2020. SARS (Severe acute respiratory syndrome). Website accessed on March 09, 2020 at
Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. The New England Journal of Medicine 367(19), 1814-1820.
Zhong NS, Zheng BJ, Li YM, Poon, Xie ZH, Chan KH. 2003. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. The Lancet 362(9393), 1353-1358.
Zumla A, Chan JFW, Azhar EI, Hui DSC, Yuen KY. 2016. Coronaviruses – drug discovery and therapeutic options. Nature Reviews – Drug Discovery 15(5), 327-347.
Remdesivir-A Possible Therapeutic Measure to Stem the Pandemic Wave.
Int. J. Biosci. 18(3), 59-73, March 2021.
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