Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

Nat Microbiol. 2020 Apr;5(4):562-569. doi: 10.1038/s41564-020-0688-y. Epub 2020 Feb 24.

Abstract

Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Betacoronavirus / chemistry
  • Betacoronavirus / classification
  • Betacoronavirus / physiology*
  • CD13 Antigens / metabolism
  • Cell Line
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / virology
  • Dipeptidyl Peptidase 4 / metabolism
  • Humans
  • Mutation
  • Pandemics
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology
  • Protein Domains
  • Receptors, Virus / chemistry
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • SARS Virus / chemistry
  • SARS Virus / physiology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Trypsin / metabolism
  • Virus Internalization*

Substances

  • Receptors, Virus
  • Recombinant Fusion Proteins
  • Spike Glycoprotein, Coronavirus
  • coronavirus receptors
  • spike glycoprotein, SARS-CoV
  • spike protein, SARS-CoV-2
  • CD13 Antigens
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2
  • Trypsin

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2