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

Cell Host Microbe. 2020 Sep 9;28(3):486-496.e6. doi: 10.1016/j.chom.2020.06.020. Epub 2020 Jul 3.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antiviral Agents / pharmacology
  • Betacoronavirus / genetics
  • Betacoronavirus / pathogenicity*
  • Betacoronavirus / physiology
  • COVID-19
  • COVID-19 Vaccines
  • Cell Line
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / therapy
  • Coronavirus Infections / virology*
  • Drug Evaluation, Preclinical
  • Host Microbial Interactions / drug effects
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / physiology
  • Humans
  • Mutation
  • Neutralization Tests
  • Pandemics / prevention & control
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / physiology
  • Pneumonia, Viral / prevention & control
  • Pneumonia, Viral / therapy
  • Pneumonia, Viral / virology*
  • Receptors, Virus / genetics
  • Receptors, Virus / physiology
  • Recombination, Genetic
  • SARS-CoV-2
  • Serine Endopeptidases / physiology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / physiology*
  • Vero Cells
  • Vesicular stomatitis Indiana virus / genetics
  • Vesicular stomatitis Indiana virus / physiology*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology
  • Virus Internalization
  • Virus Replication / genetics

Substances

  • Antiviral Agents
  • COVID-19 Vaccines
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human

Supplementary concepts

  • COVID-19 drug treatment