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

被引：100

作者：

Abdelnabi, Rana ^{[1
]}

Foo, Caroline S. ^{[1
]}

Kaptein, Suzanne J. F. ^{[1
]}

Zhang, Xin ^{[1
]}

Do, Thuc Nguyen Dan ^{[1
]}

Langendries, Lana ^{[1
]}

Vangeel, Laura ^{[1
]}

Breuer, Judith ^{[2
]}

Pang, Juanita ^{[2
]}

Williams, Rachel ^{[2
]}

Vergote, Valentijn ^{[1
]}

Heylen, Elisabeth ^{[1
]}

Leyssen, Pieter ^{[1
]}

Dallmeier, Kai ^{[1
]}

Coelmont, Lotte ^{[1
]}

Chatterjee, Arnab K. ^{[3
]}

Mols, Raf ^{[4
]}

Augustijns, Patrick ^{[4
]}

De Jonghe, Steven ^{[1
]}

Jochmans, Dirk ^{[1
]}

Weynand, Birgit ^{[5
]}

Neyts, Johan ^{[1
,6
]}

机构：

[1] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Rega Inst Med Res, Lab Virol & Chemotherapy, B-3000 Leuven, Belgium

[2] UCL Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England

[3] Calibr Scripps Res, La Jolla, CA 92037 USA

[4] Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Drug Delivery & Disposit, Box 921, B-3000 Leuven, Belgium

[5] Katholieke Univ Leuven, Dept Imaging & Pathol, Translat Cell & Tissue Res, Div Translat Cell & Tissue Res, B-3000 Leuven, Belgium

[6] Global Virus Network, GVN, Baltimore, MD 21201 USA

来源：

EBIOMEDICINE | 2021年 / 72卷

基金：

比尔及梅琳达.盖茨基金会;

关键词：

SARS-CoV-2; Antivirals; Molnupiravir; Favipiravir; hamsters; coronavirus;

D O I：

10.1016/j.ebiom.2021.103595

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：9

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