Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model.
Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model.
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DOI：
10.1172/jci.insight.160108
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发表时间：
2022-07-08
期刊：
影响因子：
8
通讯作者：
Feldmann, Heinz
中科院分区：
文献类型：
--
作者：
Rosenke, Kyle;Okumura, Atsushi;Lewis, Matthew C.;Feldmann, Friederike;Meade-White, Kimberly;Bohler, W. Forrest;Griffin, Amanda;Rosenke, Rebecca;Shaia, Carl;Jarvis, Michael A.;Feldmann, Heinz
最近出现的SARS-CoV-2 Omicron令人担忧的变种(VOC)含有一种能够逃避先前存在的免疫的严重突变的尖峰蛋白，表明继续需要干预措施。Molnupiravir(MK-4482)是一种口服核苷类似物，已证明对早期SARS-CoV-2谱系有效，最近被批准用于高危成年人感染SARS-CoV-2。在此，我们在仓鼠新冠肺炎模型中评估了MK-4482对早期阿尔法、贝塔和三角洲挥发性有机化合物和奥米克隆的疗效。与早期VOCs相关的复制和肺部疾病相比，使用赋形剂治疗的仓鼠的Omicron复制和相关肺部疾病减少。MK-4482治疗抑制了感染Alpha、Beta或Delta VOCs的仓鼠肺部的病毒复制。重要的是，MK-4482深刻地抑制了感染Omicron VOC的仓鼠上呼吸道和下呼吸道的病毒复制。与其诱变机制一致，MK-4482处理对感染滴度的抑制作用比病毒RNA基因组负荷更明显。组织病理学分析显示，在所检测的所有VOCs中，MK-4482治疗导致感染仓鼠的肺部疾病水平和病毒抗原载量随之降低。总之，我们的数据表明，MK-4482有潜力作为一种有效的抗病毒药物来对抗已知的SARS-CoV-2 VOCs，特别是Omicron，以及未来可能的SARS-CoV-2变种。
The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC), which contains a heavily mutated spike protein capable of escaping preexisting immunity, identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here, we assessed the efficacy of MK-4482 against the earlier Alpha, Beta, and Delta VOCs and Omicron in the hamster COVID-19 model. Omicron replication and associated lung disease in vehicle-treated hamsters was reduced compared with replication and lung disease associated with earlier VOCs. MK-4482 treatment inhibited virus replication in the lungs of hamsters infected with Alpha, Beta, or Delta VOCs. Importantly, MK-4482 profoundly inhibited virus replication in the upper and lower respiratory tract of hamsters infected with the Omicron VOC. Consistent with its mutagenic mechanism, MK-4482 treatment had a more pronounced inhibitory effect on infectious titers compared with viral RNA genome load. Histopathologic analysis showed that MK-4482 treatment caused a concomitant reduction in the level of lung disease and viral antigen load in infected hamsters across all VOCs examined. Together, our data indicate the potential of MK-4482 as an effective antiviral against known SARS-CoV-2 VOCs, especially Omicron, and likely future SARS-CoV-2 variants.
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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
影响因子：
64.8
作者：
Muñoz-Fontela C;Dowling WE;Funnell SGP;Gsell PS;Riveros-Balta AX;Albrecht RA;Andersen H;Baric RS;Carroll MW;Cavaleri M;Qin C;Crozier I;Dallmeier K;de Waal L;de Wit E;Delang L;Dohm E;Duprex WP;Falzarano D;Finch CL;Frieman MB;Graham BS;Gralinski LE;Guilfoyle K;Haagmans BL;Hamilton GA;Hartman AL;Herfst S;Kaptein SJF;Klimstra WB;Knezevic I;Krause PR;Kuhn JH;Le Grand R;Lewis MG;Liu WC;Maisonnasse P;McElroy AK;Munster V;Oreshkova N;Rasmussen AL;Rocha-Pereira J;Rockx B;Rodríguez E;Rogers TF;Salguero FJ;Schotsaert M;Stittelaar KJ;Thibaut HJ;Tseng CT;Vergara-Alert J;Beer M;Brasel T;Chan JFW;García-Sastre A;Neyts J;Perlman S;Reed DS;Richt JA;Roy CJ;Segalés J;Vasan SS;Henao-Restrepo AM;Barouch DH
通讯作者：
Barouch DH
DOI：
10.1093/infdis/jiab361
发表时间：
2021-09-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Abdelnabi R;Foo CS;De Jonghe S;Maes P;Weynand B;Neyts J
通讯作者：
Neyts J
与叙利亚仓鼠的富米特暴露相比，空中疾病的SARS-COV-2疾病严重程度和传播效率提高了。
影响因子：
16.6
作者：
Port JR;Yinda CK;Owusu IO;Holbrook M;Fischer R;Bushmaker T;Avanzato VA;Schulz JE;Martens C;van Doremalen N;Clancy CS;Munster VJ
通讯作者：
Munster VJ
摩尔班司米拉维尔诱导的SARS-COV-2诱变的机理。
影响因子：
16.8
作者：
Kabinger F;Stiller C;Schmitzová J;Dienemann C;Kokic G;Hillen HS;Höbartner C;Cramer P
通讯作者：
Cramer P