Antiviral treatment of COVID-19: a clinical pharmacology narrative review
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in China, has become a pandemic in March 2020. Repurposing old and relatively safe drugs becomes an advantageous option to obtain the urgently needed effective treatment. Repurposing chloroquine, hydroxychloroquine, oseltamivir, lopinavir/ritonavir, and
favipiravir, and the use of investigational drug remdesivir for treatment of COVID-19, are reviewed from the clinical pharmacology perspective, particularly its efficacy and safety. Limited clinical studies of chloroquine, hydroxychloroquine, favipiravir, and remdesivir showed some efficacy in COVID-19 treatment with tolerable adverse effects. Potential serious adverse effect of chloroquine and hydroxychloroquine is cardiac arrhythmia. Oseltamivir has no documented activity against SARS-CoV-2, while lopinavir/ritonavir showed limited efficacy in COVID-19. Currently, there is no sufficient evidence to recommend any specific anti-COVID-19 treatment. The decision to use these drugs during the COVID-19 pandemic must be based on careful consideration of the potential benefits and risks to the patient.
Downloads
References
Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3):105924. https://doi.org/10.1016/j.ijantimicag.2020.105924
World Health Organization Regional Office for Europe. WHO announces COVID-19 outbreak a pandemic [Internet]. Copenhagen: World Health Organization Regional Office for Europe; 2020 [cited 2020 Mar 26]. Available from: https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42. https://doi.org/10.1001/jama.2020.2648
Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1-23. https://doi.org/10.1007/978-1-4939-2438-7_1
Vinetz JM. Chemotherapy of malaria. In: Brunton LL, Hilal-Dandan R, Knollmann BJ, editors. Goodman & Gilman's: the pharmacological basis of therapeutics 13th ed. New York: McGraw-Hill Education. 2018. p. 976-83.
Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69. https://doi.org/10.1186/1743-422X-2-69
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71. https://doi.org/10.1038/s41422-020-0282-0
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020;57:279-83. https://doi.org/10.1016/j.jcrc.2020.03.005
Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-3. https://doi.org/10.5582/bst.2020.01047
The multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(3):185-8. Chinese. https://doi.org/10.3760/cma.j.issn.1001-0939.2020.03.009
Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020;75(7):1667-70. https://doi.org/10.1093/jac/dkaa114
Tanaka E, Taniguchi A, Urano W, Yamanaka H, Kamatani N. Pharmacogenetics of disease-modifying anti-rheumatic drugs. Best Pract Res Clin Rheumatol. 2004;18(2):233-47. https://doi.org/10.1016/j.berh.2004.02.006
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;ciaa237. https://doi.org/10.1093/cid/ciaa237
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;105949. https://doi.org/10.1016/j.ijantimicag.2020.105949
Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, et al. [A pilot study of hydroxychloroquine in treatment of patients with common coronavirus COVID-19]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;49(2):215-9. Chinese.
Acosta PE. Antiviral agents (nonretroviral). In: Brunton LL, Hilal-Dandan R, Knollmann BJ, editors. Goodman & Gilman's: the pharmacological basis of therapeutics 13th ed. New York: McGraw-Hill Education. 2018. p. 1105-16.
Dou D, Revol R, Ãstbye H, Wang H, Daniels R. Influenza A virus cell entry, replication, virion assembly and movement. Front Immunol. 2018;9:1581. https://doi.org/10.3389/fimmu.2018.01581
Dutkowski R, Thakrar B, Froehlich E, Suter P, Oo C, Ward P. Safety and pharmacology of oseltamivir in clinical use. Drug Saf. 2003;26(11):787-801. https://doi.org/10.2165/00002018-200326110-00004
Wu X, Cai Y, Huang X, Yu X, Zhao L, Wang F, et.al. Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. Emerg Infect Dis. 2020;26(6):1324-6. https://doi.org/10.3201/eid2606.200299
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. https://doi.org/10.1001/jama.2020.1585
Chandwani A, Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag. 2008;4(5):1023-33. https://doi.org/10.2147/TCRM.S3285
Jackson A, Hill A, Puls R, Else L, Amin J, Back D, et al. Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100 mg, 200/150 mg and 200/50 mg twice daily in HIV-negative volunteers. J Antimicrob Chemother. 2011;66(3):635-40. https://doi.org/10.1093/jac/dkq468
Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Comm. 2020;11(1):222. https://doi.org/10.1038/s41467-019-13940-6
Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59(3):252-6. https://doi.org/10.1136/thorax.2003.012658
Chan KS, Lai ST, Chu CM, Tsui E, Tam CY, Wong MM, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J. 2003;9(6):399-406.
Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, et al. Case of the index patient who caused tertiary transmission of coronavirus disease 2019 in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 pneumonia monitored by quantitative RT-PCR. J Korean Med Sci. 2020;35(6):e79. https://doi.org/10.3346/jkms.2020.35.e89
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99. https://doi.org/10.1056/NEJMoa2001282
Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering. [2020 Mar 18]. Retraction in: Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Engineering. [2020 Apr 02]. https://doi.org/10.1016/j.eng.2020.03.007
Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-63. https://doi.org/10.2183/pjab.93.027
Sissoko D, Laouenan C, Folkesson E, M'Lebing AB, Beavogui AH, Baize S, et al. Experimental treatment with favipiravir for Ebola virus disease (The JIKI Trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016;13(3):e1001967. https://doi.org/10.1371/journal.pmed.1002066
Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. https://doi.org/10.5582/ddt.2020.01012
Pharmaceuticals and Medical Devices Agency. Report on the Deliberation Results of Avigan tablet 200 mg. 2014. Available from: https://www.pmda.go.jp/files/000210319.pdf.
Amirian ES, Levy JK. Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses. One Health. 2020;9:100128. https://doi.org/10.1016/j.onehlt.2020.100128
World Health Organization. "Solidarity" clinical trial for COVID-19 treatments [Internet]. Geneva: World Health Organization; 2020 [updated 2020 Jun 4; cited on 2020 Jun 8]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-COVID-19-treatments.
Brown AJ, Won JJ, Graham RL, Dinnon III KH, Sims AC, Feng JY, 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. https://doi.org/10.1016/j.antiviral.2019.104541
Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396):eaal3653. https://doi.org/10.1126/scitranslmed.aal3653
Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016;531(7594):381-5. https://doi.org/10.1038/nature17180
de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, 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):6771-6. https://doi.org/10.1073/pnas.1922083117
Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 2020;382(2):2327-36. https://doi.org/10.1056/NEJMoa2007016
World Health Organization. The WHO Solidarity Trial for COVID-19 treatments officially launched in Indonesia. Geneva: World Health Organization; 2020 [updated 2020 Apr 24; cited 2020 Jun 8]. Available from: https://www.who.int/indonesia/news/detail/24-04-2020-the-who-solidarity-trial-for-covid-19-treatments-officially-launched-in-indonesia.
Mehra MR, Ruschitzka F, Patel AN. Retraction-Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020;395(10240):1820. https://doi.org/10.1016/S0140-6736(20)31324-6
Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial on hydroxychloroquine, 5 June 2020. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. [updated 2020 Jun 5; cited 2020 Jun 8]. Available from: https://www.recoverytrial.net/files/hcq-recovery-statement-050620-final-002.pdf/@@download.
Copyright (c) 2020 Instiaty, I Gusti Agung Ayu Putu Sri Darmayani, Jefman Efendi Marzuki, Ferina Angelia, William, Angelina Siane, Lela Dwi Sary, Lina Yohanes, Reni Widyastuti, Riki Nova, Dewi Sharon Simorangkir, Lonah, Yolanda Safitri, Gestina Aliska, Anggi Gayatri
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.