Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

Science. 2020 Nov 13;370(6518):856-860. doi: 10.1126/science.abd2985. Epub 2020 Oct 20.

Abstract

The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Monoclonal / immunology
  • Betacoronavirus / genetics
  • Betacoronavirus / physiology*
  • COVID-19
  • Caco-2 Cells
  • Coronavirus Infections / virology*
  • Female
  • HEK293 Cells
  • Host Microbial Interactions
  • Humans
  • Lung / metabolism
  • Male
  • Metal Nanoparticles
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neuropilin-1 / chemistry
  • Neuropilin-1 / genetics
  • Neuropilin-1 / immunology
  • Neuropilin-1 / metabolism*
  • Neuropilin-2 / metabolism
  • Olfactory Mucosa / metabolism
  • Olfactory Mucosa / virology
  • Pandemics
  • Peptide Fragments / metabolism
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / virology*
  • Protein Binding
  • Protein Domains
  • Respiratory Mucosa / metabolism
  • SARS-CoV-2
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Virus Internalization*

Substances

  • Antibodies, Monoclonal
  • NRP1 protein, human
  • Neuropilin-2
  • Peptide Fragments
  • Spike Glycoprotein, Coronavirus
  • neuropilin-2, human
  • spike protein, SARS-CoV-2
  • Neuropilin-1
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human