Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model.
Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model.
复制标题
DOI：
10.1038/s41467-021-21992-w
复制
发表时间：
2021-03-19
影响因子：
16.6
通讯作者：
Nougairède A
中科院分区：
文献类型：
--
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
尽管没有临床前证据或临床前证据有限，但在临床试验中对重新利用的药物进行了大规模评估，以缓解针对 SARS-CoV-2 的抗病毒分子的缺乏。在这里，我们使用叙利亚仓鼠模型来评估法匹拉韦的抗病毒功效，了解其作用机制并确定其药代动力学。当在感染之前或同时开始治疗时，法匹拉韦具有很强的剂量效应，导致肺部感染滴度降低并临床缓解疾病。法匹拉韦的抗病毒作用与病毒基因组中掺入大量突变和病毒感染性降低有关。血浆药物暴露达到的抗病毒功效与之前在人体临床试验中发现的相当。值得注意的是，所测试的法匹拉韦的最高剂量与动物的毒性迹象有关。因此，需要进行药代动力学和耐受性研究来确定是否可以在人体中安全地实现类似的效果。法匹拉韦对多种 RNA 病毒具有广谱抗病毒活性。在这里，作者在叙利亚仓鼠感染模型中研究了不同药物剂量的安全性、药代动力学和抗 SARS-CoV-2 功效，并结合遗传分析，他们表明高剂量的法匹拉韦会降低病毒感染性，同时诱导病毒基因组中出现突变，从而降低适应性。
Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans. Favipiravir has broad-spectrum antiviral activity against a variety of RNA viruses. Here the authors investigate the safety, pharmacokinetics and anti-SARS-CoV-2 efficacy of different drug dosage in the a Syrian hamster model of infection and, combined with genetic analyses, they show that Favipiravir at high doses decrease viral infectivity while inducing the emergence of mutations in viral genomes, decreasing fitness.
登录
查看更多内容
法匹拉韦在病毒体内复制过程中引发抗病毒突变。
影响因子：
7.7
作者：
Arias A;Thorne L;Goodfellow I
通讯作者：
Goodfellow I
影响因子：
4.9
作者：
Julander, Justin G.;Shafer, Kristiina;Furuta, Yousuke
通讯作者：
Furuta, Yousuke
影响因子：
15.9
作者：
Mercorelli B;Palù G;Loregian A
通讯作者：
Loregian A
影响因子：
4.9
作者：
Madelain, Vincent;Guedj, Jeremie;Raoul, Herve
通讯作者：
Raoul, Herve
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