What is the role of molnupiravir and favipiravir in the treatment of coronavirus disease 2019 (COVID-19)?

Updated: Jun 25, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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Investigational Antivirals


Molnupiravir (MK-4482 [previously EIDD-2801]; Merck) is an oral antiviral agent that is a prodrug of the nucleoside derivative N4-hydroxycytidine. It elicits antiviral effects by introducing copying errors during viral RNA replication of the SARS-CoV-2 virus. Preliminary results from the phase 2a dose-ranging MOVe-OUT study (n = 202) showed at an average of 10 days after symptom onset, 24% of outpatients in the placebo group remained culture positive for SARS-CoV-2; whereas, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients. The inpatient molnupiravir study (MOVe-IN) has been halted, but the phase 3 trial in outpatients who have at least 1 risk factor for poor outcomes (eg, advanced age, obesity, diabetes) will proceed with patients receiving 800 mg orally twice daily. [161]  


Favipiravir (Avigan; Appili Therapeutics) is an oral antiviral approved for treatment of influenza in Japan. It is approved in Russia for treatment of COVID-19.

Favipiravir selectively inhibits RNA polymerase, which is necessary for viral replication. An adaptive, multicenter, open label, randomized, phase 2/3 clinical trial of favipiravir compared with standard of care I hospitalized patients with moderate COVID-19 was conducted in Russia. Both dosing regimens of favipiravir demonstrated similar virologic response. Viral clearance on Day 5 was achieved in 25/40 (62.5%) patients on in the favipiravir group compared with 6/20 (30%) patients in the standard care group (p = 0.018). Viral clearance on Day 10 was achieved in 37/40 (92.5%) patients taking favipiravir compared with 16/20 (80%) in the standard care group (p = 0.155). [162]  

In the United States, the phase 3 PRESECO (Preventing Severe COVID Disease) study is evaluating use in patients with mild-to-moderate symptoms to prevent disease progression and hospitalization. The phase 3 PEPCO (Post Exposure Prophylaxis for COVID-19) study will look at asymptomatic individuals with direct exposure (within 72 hours) to an infected individual. A study in hospitalized patients is also underway. [163, 164]  Additionally, the phase 2 CONTROL study is evaluating use to control outbreaks of COVID-19 in Canadian long-term care facilities. [165]

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