The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model

EBioMedicine. 2021 Oct;72:103595. doi: 10.1016/j.ebiom.2021.103595. Epub 2021 Sep 24.


Background: Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. First efficacy data have been recently reported in COVID-19 patients.

Methods: We here report on the combined antiviral effect of both drugs in a SARS-CoV-2 Syrian hamster infection model. The infected hamsters were treated twice daily with the vehicle (the control group) or a suboptimal dose of each compound or a combination of both compounds.

Findings: When animals were treated with a combination of suboptimal doses of Molnupiravir and Favipiravir at the time of infection, a marked combined potency at endpoint is observed. Infectious virus titers in the lungs of animals treated with the combination are reduced by ∼5 log10 and infectious virus are no longer detected in the lungs of >60% of treated animals. When start of treatment was delayed with one day a reduction of titers in the lungs of 2.4 log10 was achieved. Moreover, treatment of infected animals nearly completely prevented transmission to co-housed untreated sentinels. Both drugs result in an increased mutation frequency of the remaining viral RNA recovered from the lungs of treated animals. In the combo-treated hamsters, an increased frequency of C-to-T mutations in the viral RNA is observed as compared to the single treatment groups which may explain the pronounced antiviral potency of the combination.

Interpretation: Our findings may lay the basis for the design of clinical studies to test the efficacy of the combination of Molnupiravir/Favipiravir in the treatment of COVID-19.

Funding: stated in the acknowledgment.

Keywords: Antivirals; Favipiravir, hamsters, coronavirus; Molnupiravir; SARS-CoV-2.

MeSH terms

  • Amides / pharmacology
  • Amides / therapeutic use*
  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • COVID-19 / transmission
  • COVID-19 Drug Treatment*
  • Cytidine / analogs & derivatives*
  • Cytidine / pharmacology
  • Cytidine / therapeutic use
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Female
  • Hydroxylamines / pharmacology
  • Hydroxylamines / therapeutic use*
  • Lung / virology*
  • Mesocricetus
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • RNA, Viral
  • Treatment Outcome
  • Viral Load


  • Amides
  • Antiviral Agents
  • Hydroxylamines
  • Pyrazines
  • RNA, Viral
  • Cytidine
  • favipiravir
  • molnupiravir