The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model.
The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model.
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DOI：
10.1016/j.ebiom.2021.103595
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发表时间：
2021-10
期刊：
影响因子：
11.1
通讯作者：
Neyts J
中科院分区：
文献类型：
--
作者：
Abdelnabi R;Foo CS;Kaptein SJF;Zhang X;Do TND;Langendries L;Vangeel L;Breuer J;Pang J;Williams R;Vergote V;Heylen E;Leyssen P;Dallmeier K;Coelmont L;Chatterjee AK;Mols R;Augustijns P;De Jonghe S;Jochmans D;Weynand B;Neyts J
法匹拉韦和莫努匹拉韦是口服抗病毒药物，据报道可对SARS-CoV-2发挥抗病毒活性。最近报告了COVID-19患者的首个疗效数据。我们在此报告了两种药物在SARS-CoV-2叙利亚仓鼠感染模型中的联合抗病毒作用。每天两次用媒介物（对照组）或每种化合物的次优剂量或两种化合物的组合处理感染的仓鼠。当在感染时用次优剂量的莫努匹拉韦和法匹拉韦组合治疗动物时，在终点观察到显著的组合效力。用该组合处理的动物的肺中的感染性病毒滴度降低了105 log 10，并且在>60%的处理动物的肺中不再检测到感染性病毒。当治疗开始延迟一天时，肺部滴度降低2.4 log 10。此外，对受感染动物的治疗几乎完全防止了向共同饲养的未经治疗的哨兵的传播。这两种药物导致从治疗动物的肺中回收的剩余病毒RNA的突变频率增加。在组合处理的仓鼠中，与单一处理组相比，观察到病毒RNA中C至T突变的频率增加，这可以解释组合的显著抗病毒效力。释义：我们的发现可能为临床研究的设计奠定基础，以测试莫努匹拉韦/法匹拉韦联合治疗COVID-19的疗效。资金：在确认中说明。
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. 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. 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.
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影响因子：
16.6
作者：
Rosenke K;Hansen F;Schwarz B;Feldmann F;Haddock E;Rosenke R;Barbian K;Meade-White K;Okumura A;Leventhal S;Hawman DW;Ricotta E;Bosio CM;Martens C;Saturday G;Feldmann H;Jarvis MA
通讯作者：
Jarvis MA
DOI：
10.1073/pnas.2014441117
发表时间：
2020-10-27
影响因子：
11.1
作者：
Kaptein SJF;Jacobs S;Langendries L;Seldeslachts L;Ter Horst S;Liesenborghs L;Hens B;Vergote V;Heylen E;Barthelemy K;Maas E;De Keyzer C;Bervoets L;Rymenants J;Van Buyten T;Zhang X;Abdelnabi R;Pang J;Williams R;Thibaut HJ;Dallmeier K;Boudewijns R;Wouters J;Augustijns P;Verougstraete N;Cawthorne C;Breuer J;Solas C;Weynand B;Annaert P;Spriet I;Vande Velde G;Neyts J;Rocha-Pereira J;Delang L
通讯作者：
Delang L
影响因子：
4.5
作者：
Mayor J;Engler O;Rothenberger S
通讯作者：
Rothenberger S
影响因子：
16.6
作者：
Driouich JS;Cochin M;Lingas G;Moureau G;Touret F;Petit PR;Piorkowski G;Barthélémy K;Laprie C;Coutard B;Guedj J;de Lamballerie X;Solas C;Nougairède A
通讯作者：
Nougairède A
QualiMap 2：高通量测序数据的高级多样本质量控制。
DOI：
10.1093/bioinformatics/btv566
发表时间：
2016-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Okonechnikov K;Conesa A;García-Alcalde F
通讯作者：
García-Alcalde F