Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV

Nat Commun. 2020 Mar 27;11(1):1620. doi: 10.1038/s41467-020-15562-9.

Abstract

Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / immunology*
  • Betacoronavirus / chemistry
  • Betacoronavirus / immunology
  • Betacoronavirus / physiology*
  • Broadly Neutralizing Antibodies / immunology*
  • Calcium Channels / metabolism
  • Cathepsin L / metabolism
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / metabolism
  • Cell Fusion
  • Coronavirus Infections / immunology
  • Cross Reactions
  • Endocytosis
  • Giant Cells / physiology
  • HEK293 Cells
  • Humans
  • Neutralization Tests
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pneumonia, Viral / immunology
  • Protein Domains
  • Protein Multimerization
  • Receptors, Virus / metabolism
  • SARS Virus / immunology
  • Severe Acute Respiratory Syndrome / immunology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Trypsin / metabolism
  • Virus Internalization*

Substances

  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • Calcium Channels
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • TPCN2 protein, human
  • spike glycoprotein, SARS-CoV
  • spike protein, SARS-CoV-2
  • PIKFYVE protein, human
  • Cathepsins
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2
  • Trypsin
  • Cathepsin L

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2