Host Cell Entry and Neutralization Sensitivity of SARS-CoV-2 Lineages B.1.620 and R.1

Viruses. 2022 Nov 9;14(11):2475. doi: 10.3390/v14112475.

Abstract

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitates viral entry into host cells and is the key target for neutralizing antibodies. The SARS-CoV-2 lineage B.1.620 carries fifteen mutations in the S protein and is spread in Africa, the US and Europe, while lineage R.1 harbors four mutations in S and infections were observed in several countries, particularly Japan and the US. However, the impact of the mutations in B.1.620 and R.1 S proteins on antibody-mediated neutralization and host cell entry are largely unknown. Here, we report that these mutations are compatible with robust ACE2 binding and entry into cell lines, and they markedly reduce neutralization by vaccine-induced antibodies. Our results reveal evasion of neutralizing antibodies by B.1.620 and R.1, which might have contributed to the spread of these lineages.

Keywords: ACE2 binding; B.1.620; R.1; SARS-CoV-2; antibody evasion; cell entry; neutralization; spike protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19*
  • Humans
  • Mutation
  • Peptidyl-Dipeptidase A / metabolism
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus
  • Virus Internalization

Substances

  • Spike Glycoprotein, Coronavirus
  • Angiotensin-Converting Enzyme 2
  • Peptidyl-Dipeptidase A
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • spike protein, SARS-CoV-2

Grants and funding

This research was funded by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung), grant numbers 1KI2074A (NK), 01KI2006D (SP), 01KI20328A (SP), 01KX2021 (SP), 01KI2043 (H-MJ), NaFoUniMedCOVID19-COVIM: 01KX2021 (H-MJ), the Ministry for Science and Culture of Lower Saxony (Niedersächsisches Ministerium für Wissenschaft und Kultur), grant numbers 14-76103-184 (SP) and MWK HZI COVID-19 (SP), the Bavarian State Ministry for Science and the Arts (Bayerisches Staatsministerium für Wissenschaft und Kunst), grant number RTG1660 (H-MJ), the German Research Foundation (Deutsche Forschungsgemeinschaft), grant numbers PO 716/11-1 (SP), PO 716/14-1 (SP) and TRR130 (H-MJ), the German Center for Infection Research, grant number 80018019238 (GMNB), and the European Regional Development Fund, grant number Defeat Corona: ZW7-8515131 (GMNB).