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Antiviral drugs for COVID-19

In the course of the COVID-19 pandemic, three antiviral drugs have been developed, which use different mechanisms to inhibit the replication of the virus. Molnupiravir and remdesivir are polymerase inhibitors, while nirmatrelvir is a protease inhibitor. Randomised studies have shown that these antiviral drugs, provided they are administered within 5 to 7 days after the first COVID-19 symptoms have appeared, significantly reduce the risk of hospitalisation and mortality in unvaccinated patients at elevated risk of a severe disease course. 

  • Administering the polymerase inhibitors molnupiravir or remdesivir or the protease inhibitor nirmatrelvir to unvaccinated patients in the early stages of COVID-19 can reduce the numbers of hospitalisations and deaths.
  • No published studies have compared the effectiveness of these antiviral drugs. An indirect comparison is impossible since the placebo-controlled studies differ too much from each other. 
  • For now, the applications for these antiviral drugs appear to be limited. There are theoretical arguments for using them in immunocompromised patients as an alternative to monoclonal antibodies.

  1. Burki TK. The role of antiviral treatment in the COVID-19 pandemic. Lancet Respir Med. 2022 Feb;10(2):e18. doi: 10.1016/S2213-2600(22)00011-X.
  2. Fan H, Lou F, Fan J, Li M, Tong Y. The emergence of powerful oral anti-COVID-19 drugs in the post-vaccine era. Lancet Microbe. 2022 Feb;3(2):e91. doi: 10.1016/S2666-5247(21)00278-0.
  3. Cully M. A tale of two antiviral targets - and the COVID-19 drugs that bind them. Nat Rev Drug Discov. 2022 Jan;21(1):3-5. doi: 10.1038/d41573-021-00202-8. 
  4. Stolk LM. Direct werkende antivirale middelen bij chronische hepatitis C. Gebu. 2022;56(2):9-12
  5. EMA. Annex I: conditions of use, conditions for distribution and patients targeted and conditions for safety monitoring adressed to member states for unauthorised product Lagevrio (molnupiravir). Available from:
  6. Productinformatie Veklury. Available from: Accessed 21-02-2022.
  7. Productinformatie Paxlovid. Available from: Accessed 08-02-2022.
  8. Ader F, Bouscambert-Duchamp M, Hites M, Peiffer-Smadja N, Poissy J, Belhadi D, et al. DisCoVeRy Study Group. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. Lancet Infect Dis. 2022 Feb;22(2):209-221. doi: 10.1016/S1473-3099(21)00485-0. 
  9. Malone B, Campbell EA. Molnupiravir: coding for catastrophe. Nat Struct Mol Biol. 2021 Sep;28(9):706-708. doi: 10.1038/s41594-021-00657-8. Erratum in: Nat Struct Mol Biol. 2021 Nov;28(11):955. 
  10. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. MOVe-OUT Study Group. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022 Feb 10;386(6):509-520. doi: 10.1056/NEJMoa2116044. 
  11. Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. GS-US-540-9012 (PINETREE) Investigators. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. 
  12. National Institute of Allergy and Infectious Diseases. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. Available from: Accessed 10-02-2022
  13. Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et al. EPIC-HR Investigators. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022 Apr 14;386(15):1397-1408. doi: 10.1056/NEJMoa2118542. 


  • Leo M.L. Stolk, dr