期刊
EBIOMEDICINE
卷 72, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2021.103595
关键词
SARS-CoV-2; Antivirals; Molnupiravir; Favipiravir, hamsters, coronavirus
资金
- Covid-19-Fund KU Leuven/UZ Leuven
- COVID-19 call of FWO [G0G4820N]
- European Union [101003627, 812673]
- Bill & Melinda Gates Foundation (BGMF) [INV00636]
- KU Leuven internal project fund
- China Scholarship Council [201906170033]
- NIHR UCL/UCLH Biomedical Research Centre
- Rosetrees Trust
- Marie Curie Actions (MSCA) [812673] Funding Source: Marie Curie Actions (MSCA)
The combination of Molnupiravir and Favipiravir demonstrated a significant antiviral effect in a Syrian hamster model infected with SARS-CoV-2, reducing infectious virus titers in the lungs and preventing transmission to co-housed untreated sentinels. Mutation frequency in the viral RNA recovered from the lungs of treated animals increased, with a higher frequency of C-to-T mutations observed in the combo treatment group, explaining the pronounced antiviral potency of the combination.
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 similar to 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. (C) 2021 The Author(s). Published by Elsevier B.V.
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