The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model.
EBioMedicine
; 72: 103595, 2021 Oct.
Article
in English
| MEDLINE | ID: covidwho-1433162
ABSTRACT
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 â¼5 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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pyrazines
/
Cytidine
/
Amides
/
COVID-19 Drug Treatment
/
Hydroxylamines
/
Lung
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Limits:
Animals
Language:
English
Journal:
EBioMedicine
Year:
2021
Document Type:
Article
Affiliation country:
J.ebiom.2021.103595
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