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A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2020-07-03 , DOI: 10.1016/j.chom.2020.06.020
M Eugenia Dieterle 1 , Denise Haslwanter 1 , Robert H Bortz 1 , Ariel S Wirchnianski 2 , Gorka Lasso 1 , Olivia Vergnolle 3 , Shawn A Abbasi 4 , J Maximilian Fels 1 , Ethan Laudermilch 1 , Catalina Florez 5 , Amanda Mengotto 6 , Duncan Kimmel 6 , Ryan J Malonis 3 , George Georgiev 3 , Jose Quiroz 6 , Jason Barnhill 7 , Liise-Anne Pirofski 8 , Johanna P Daily 8 , John M Dye 4 , Jonathan R Lai 3 , Andrew S Herbert 9 , Kartik Chandran 1 , Rohit K Jangra 1
Affiliation  

There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals. Here, we generate a highly infectious recombinant vesicular stomatitis virus (VSV) bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. The neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in a high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S, and neutralization of rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific therapeutics and for mechanistic studies of viral entry and its inhibition.



中文翻译:

一种具有复制能力的水泡性口腔炎病毒,用于研究SARS-CoV-2穗介导的细胞进入及其抑制作用。

迫切需要预防和治疗COVID-19的疫苗和治疗剂。SARS-CoV-2快速对策的发展取决于健壮,可扩展且易于部署的替代病毒检测方法的可用性,以筛选抗病毒体液反应,定义免疫保护的相关性以及选择候选抗病毒剂。在这里,我们产生了以SARS-CoV-2穗状糖蛋白S作为唯一进入糖蛋白的高度感染性重组水疱性口炎病毒(VSV),并表明该重组病毒rVSV-SARS-CoV-2 S与SARS-CoV非常相似-2在其与条目相关的属性中。可以使用rVSV-SARS-CoV-2 S在高通量荧光报告基因分析中评估一大批COVID-19恢复期血清的中和活性,这些抗血清中的刺突特异性抗体与rVSV-SARS-CoV-2 S和真正的SARS-CoV-2的中和作用高度相关。我们的发现强调了rVSV-SARS-CoV-2 S在开发突波特异性疗法以及病毒进入及其抑制机制方面的实用性。

更新日期:2020-09-10
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