Cell Host & Microbe
Volume 28, Issue 3, 9 September 2020, Pages 486-496.e6
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A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition

https://doi.org/10.1016/j.chom.2020.06.020Get rights and content
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Highlights

  • Highly infectious recombinant VSV expressing SARS-CoV-2 spike (S) was generated

  • rVSV-SARS-CoV-2 S resembles SARS-CoV-2 in entry and inhibitor or antibody sensitivity

  • rVSV-SARS-CoV-2 S affords rapid screens and forward-genetic analyses of antivirals

Summary

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.

Keywords

VSV
surrogate
COVID-19
SARS-CoV-2
neutralization assay
ACE2
neutralizing antibody
serology
antiviral drugs
convalescent plasma

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These authors contributed equally