Join us   Log in  

PHARMASPIRE - Volume 13, Issue 3, July - September, 2021

Pages: 77-85

Date of Publication: 07-Jun-2022

Print Article   Download XML  Download PDF

Molnupiravir – A prospective silver bullet to mitigate severe acute respiratory syndrome corona virus-2

Author: Meenakshi Negi , Pooja A. Chawla, Ghanshyam Teli , Abdul Faruk , Viney Chawla

Category: Pharmaceutics


The whole world is eagerly waiting for the unearthing of the best treatment strategy to put an end to the prevailing coronavirus disease-2019 pandemic. The pathogen responsible for this disease, that is, severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) continues to be the most challenging issue that has kept the researchers and innovators all over the world in a dilemma of resolving it through finding the most efficacious, safe, and cost-effective therapy. A large number of drugs are under investigation as a part of drug repurposing approach for the treatment of SARS-CoV-2. One such drug, molnupiravir, is under Phase II/III clinical trials against SARS-CoV-2. Through this work, the authors will give an insight into the various aspects of molnupiravir as an antiviral agent including chemistry, pharmacokinetics, synthetic route, in vitro, in vivo studies, clinical trials, and probable mode of antiviral action of molnupiravir against SARS-CoV-2. The molecular docking approach has also been used to evaluate the binding interactions of the active form of molnupiravir, N-4-hydroxycytidine, with the RNA-dependent RNA polymerase of SARS-CoV-2 which emphasized on its good binding potential with the active site residues displaying a binding energy of ?6.4 kcal per mol.

Keywords: Molnupiravir, severe acute respiratory syndrome coronavirus-2, clinical trials, docking studies


1. Fan Y, Zhao K, Shi Z, Zhou P. Bat Coronaviruses in China. Viruses 2019;11:1-14.

2. Negi M, Chawla PA, Faruk A, Chawla V. Role of heterocyclic compounds in SARS and SARS CoV-2 pandemic. Bioorg Chem 2020;104:1-36.

3. Kong R, Yang G, Xue R, Liu M, Wang F, Hu J, et al. COVID-19 docking server: An interactive server for docking small molecules, peptides and antibodies against potential targets of COVID-19. Bioinformatics 2020;36:5109-111.

4. Report of the WHO-China Joint Mission on Coronavirus Disease 2019. Geneva: World Health Organization; 2020. Available from: https://www.who. int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf. [Last accessed on 2020 Dec 16].

5. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. Correspondence: The proximal origin of SARS-CoV-2. Nat Med 2020;26:450-2.

6. Liu X, Li Z, Liu S, Sun J, Chen Z, Jiang M, et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B 2020;811:1-11.

7. Shah B, Modi P, Sagar SR. In silico studies on therapeutic agents for COVID-19: Drug repurposing approach. Life Sci 2020;252:1-12.

8. Thakur S, Sarkar BM, Ansari AJ, Khandelwal A, Arya A, Poduri R, et al. Exploring the magic bullets to identify Achilles’ heel in SARS-CoV-2: Delving deeper into the sea of possible therapeutic options in COVID-19 disease: An update. Food Chem Toxicol 2021;147:1-21.

9. Wang Y, Anirudhan V, Du R, Cui Q, Rong L. RNA-dependent RNA polymerase of SARS-CoV-2 as a therapeutic target. J Med Virol 2021;93:300-10.

10. Toots M, Yoon J, Cox RM, Hart M, Sticher ZM, Makhsous N, et al. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci Transl Med 2019;11:1-13.

11. Toots M, Yoon J, Hart M, Natchus MG, Painter GR, Plemper RK. Quantitative efficacy paradigms of the influenza clinical drug candidate EIDD-2801 in the ferret model. Transl Res 2020;218:16-28.

12. COVID-19 First in Human Study to Evaluate Safety, Tolerability, and Pharmacokinetics of EIDD-2801 in Healthy Volunteers; 2020. Available from: [Last accessed on 2020 Dec 16].

13. Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants with COVID-19 (MK-4482-001); 2020. Available from: https:// and cond=covid19 and draw=2 and rank=4. [Last accessed on 2020 Dec 16].

14. Cox RM, Wolf JD, Plemper RK. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol 2021;6:11-8.

15. Cevik M, Kuppalli K, Kindrachuk J, Peiris M. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 2020;371:1-6.

16. Shang Z, Chan SY, Liu WJ, Li P, Huang W. Recent insights into emerging Coronavirus: SARS-CoV2. ACS Infect Dis 2020.

17. Forstera P, Forsterd L, Renfrewb C, Forsterc M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proc Natl Acad Sci U S A 2020;117:9241-3.

18. Azer SA. COVID-19: Pathophysiology, diagnosis, complications and investigational therapeutics. New Microbes New Infect 2020;37:100738.

19. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol 2020;215:108427.

20. Vallamkondu J, John A, Wani WY, Ramadevi RS, Jella KK, Reddy PH, et al. SARS-CoV-2 pathophysiology and assessment of Coronaviruses in CNS diseases with a focus on therapeutic targets. Biochim Biophys Acta Mol Basis Dis 2020;1866:165889.

21. Parasher A. COVID-19: Current understanding of its pathophysiology, clinical presentation and treatment. Postgrad Med J 2020;97:312-20.

22. Hampton T. New flu antiviral candidate may thwart drug resistance. JAMA 2020;323:17.

23. Steiner A, Znidar D, Otvos SB, Snead DR, Dallinger D, Kappe CO. A highyielding synthesis of EIDD-2801 from uridine. European J Org Chem 2020;22:6736-9.

24. Urakova N, Kuznetsova V, Crossman DK, Sokratian A, Guthrie DB, KolykhalovAA, et al. β-D-N4-Hydroxycytidine is a potent anti-alphavirus compound that induces a high level of mutations in the viral genome. JVirol 2018;92:e01965-17.

25. Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, Agostini ML, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med 2020;12:eabb5883.

26. Abdelnabi R, Foo CS, Kaptein SJ, Zhang X, Langendries L, Vangeel L, et al. Molnupiravir (EIDD-2801) Inhibits SARS-CoV2 Replication in Syrian Hamsters Model, bioRxiv; 2020.

27. Ahmad J, Ikram S, Ahmad F, Rehman IU, Mushtaq M. SARS-CoV-2 RNA dependent RNA polymerase (RdRp)-a drug repurposing study. Heliyon 2020;6:e04502.

28. Painter WP, Holman W, Bush JA, Almazedi F, Malik H, Eraut NC, et al. Human Safety, Tolerability, and Pharmacokinetics of a Novel Broad-Spectrum Oral Antiviral Compound, Molnupiravir, with Activity Against SARS-CoV-2, medRxiv; 2020.

29. Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants with COVID-19 (MK-4482-001); 2020. Available from: https:// and cond=covid19 and draw=2 and rank=1. [Last accessed on 2020 Dec 16].

30. Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants with COVID-19 (MK-4482-002); 2020. Available from: https:// and cond=covid19 and draw=2 and rank=2. [Last accessed on 2020 Dec 16].

31. A Safety, Tolerability and Efficacy of Molnupiravir (EIDD-2801) to Eliminate Infectious Virus Detection in Persons; 2020. Available from: https:// and cond=covid19 and draw=2 and rank=3. [Last accessed on 2020 Dec 16]