A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition

A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition
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一株复制型水泡性口炎病毒用于研究SARS-CoV-2刺突介导的细胞侵入及其抑制作用

DOI:
10.1016/j.chom.2020.06.020
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发表时间:
2020-09-09
影响因子:
30.3
通讯作者:
Jangra, Rohit K.
Jangra, Rohit K.
中科院分区:
医学1区
文献类型:
--
作者:
Dieterle, M. Eugenia;Haslwanter, Denise;Jangra, Rohit K.

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目前迫切需要疫苗和治疗方法来预防和治疗COVID-19,快速制定SARS-CoV-2对策取决于是否有强大的、可扩展的、易于部署的替代病毒检测方法,以筛选抗病毒体液反应,确定免疫保护的相关因素,并筛选候选抗病毒药物。在这里,我们产生了一种具有高度传染性的重组水疱性口炎病毒(VSV),其携带SARS-CoV-2刺突糖蛋白S作为其唯一的进入糖蛋白,并表明该重组病毒rvsv - sars - cov - 2s在其进入相关特性方面与SARS-CoV-2非常相似。用rvsv - sars - cov - 2s进行高通量荧光报告试验,可以评估大量COVID-19恢复期血清的中和活性,这些抗血清中的尖峰特异性抗体对rvsv - sars - cov - 2s和真实SARS-CoV-2的中和作用高度相关。我们的研究结果强调了rvsv - sars - cov - 2s在开发刺突特异性治疗方法以及病毒进入及其抑制的机制研究中的实用性。
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.