tetano
Editor, Senior Moderator
EBioMedicine
. 2021 Sep 24;72:103595.
doi: 10.1016/j.ebiom.2021.103595. Online ahead of print.
The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model
Rana Abdelnabi[SUP] 1 [/SUP], Caroline S Foo[SUP] 1 [/SUP], Suzanne J F Kaptein[SUP] 1 [/SUP], Xin Zhang[SUP] 1 [/SUP], Thuc Nguyen Dan Do[SUP] 1 [/SUP], Lana Langendries[SUP] 1 [/SUP], Laura Vangeel[SUP] 1 [/SUP], Judith Breuer[SUP] 2 [/SUP], Juanita Pang[SUP] 2 [/SUP], Rachel Williams[SUP] 2 [/SUP], Valentijn Vergote[SUP] 1 [/SUP], Elisabeth Heylen[SUP] 1 [/SUP], Pieter Leyssen[SUP] 1 [/SUP], Kai Dallmeier[SUP] 1 [/SUP], Lotte Coelmont[SUP] 1 [/SUP], Arnab K Chatterjee[SUP] 3 [/SUP], Raf Mols[SUP] 4 [/SUP], Patrick Augustijns[SUP] 4 [/SUP], Steven De Jonghe[SUP] 1 [/SUP], Dirk Jochmans[SUP] 1 [/SUP], Birgit Weynand[SUP] 5 [/SUP], Johan Neyts[SUP] 6 [/SUP]
Affiliations
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 ∼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.
. 2021 Sep 24;72:103595.
doi: 10.1016/j.ebiom.2021.103595. Online ahead of print.
The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model
Rana Abdelnabi[SUP] 1 [/SUP], Caroline S Foo[SUP] 1 [/SUP], Suzanne J F Kaptein[SUP] 1 [/SUP], Xin Zhang[SUP] 1 [/SUP], Thuc Nguyen Dan Do[SUP] 1 [/SUP], Lana Langendries[SUP] 1 [/SUP], Laura Vangeel[SUP] 1 [/SUP], Judith Breuer[SUP] 2 [/SUP], Juanita Pang[SUP] 2 [/SUP], Rachel Williams[SUP] 2 [/SUP], Valentijn Vergote[SUP] 1 [/SUP], Elisabeth Heylen[SUP] 1 [/SUP], Pieter Leyssen[SUP] 1 [/SUP], Kai Dallmeier[SUP] 1 [/SUP], Lotte Coelmont[SUP] 1 [/SUP], Arnab K Chatterjee[SUP] 3 [/SUP], Raf Mols[SUP] 4 [/SUP], Patrick Augustijns[SUP] 4 [/SUP], Steven De Jonghe[SUP] 1 [/SUP], Dirk Jochmans[SUP] 1 [/SUP], Birgit Weynand[SUP] 5 [/SUP], Johan Neyts[SUP] 6 [/SUP]
Affiliations
- PMID: 34571361
- DOI: 10.1016/j.ebiom.2021.103595
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 ∼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.