Antiviral treatment of COVID-19: a clinical pharmacology narrative review

  • Instiaty Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0002-8958-5441
  • I Gusti Agung Ayu Putu Sri Darmayani Postgraduate Student of Clinical Pharmacology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Jefman Efendi Marzuki Postgraduate Student of Clinical Pharmacology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0002-0776-2417
  • Ferina Angelia The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia https://orcid.org/0000-0002-0220-837X
  • William The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia https://orcid.org/0000-0003-2475-4934
  • Angelina Siane The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia https://orcid.org/0000-0001-7964-6899
  • Lela Dwi Sary The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia https://orcid.org/0000-0002-1981-5870
  • Lina Yohanes Postgraduate Student of Clinical Pharmacology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Reni Widyastuti The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia
  • Riki Nova The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia
  • Dewi Sharon Simorangkir The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia
  • Lonah The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia
  • Yolanda Safitri Postgraduate Student of Clinical Pharmacology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0001-7724-1564
  • Gestina Aliska The Indonesian Clinical Pharmacology Association (PERDAFKI), Jakarta, Indonesia
  • Anggi Gayatri Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Keywords: COVID-19, favipiravir, hydroxychloroquine, lopinavir, oseltamivir, remdesivir
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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.

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References

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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.

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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.

  33. 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

  34. 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.

  35. 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

  36. 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

  37. 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

  38. 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

  39. 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

  40. 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.

  41. 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

  42. 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.

Published
2020-07-18
How to Cite
1.
Instiaty, Darmayani IGAAPS, Marzuki JE, Angelia F, William, Siane A, Sary LD, Yohanes L, Widyastuti R, Nova R, Simorangkir DS, Lonah, Safitri Y, Aliska G, Gayatri A. Antiviral treatment of COVID-19: a clinical pharmacology narrative review. Med J Indones [Internet]. 2020Jul.18 [cited 2024Oct.11];29(3):332-45. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/4652
Section
Review Article