The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity

Cell. 2020 Sep 3;182(5):1284-1294.e9. doi: 10.1016/j.cell.2020.07.012. Epub 2020 Jul 17.


The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here, we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.

Keywords: COVID-19; SARS-CoV-2; glycosylation; mutants; pseudotyped virus; spike; variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antigens, Viral / genetics*
  • Antigens, Viral / immunology
  • Betacoronavirus / genetics
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity*
  • Binding Sites
  • Cattle
  • Chlorocebus aethiops
  • Cricetinae
  • Dogs
  • Glycosylation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Macaca mulatta
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mutation*
  • RAW 264.7 Cells
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Swine
  • Vero Cells
  • Virulence / genetics


  • Antigens, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2