N121T and N121S substitutions on the SARS-CoV-2 spike protein impact on serum neutralization

J Med Virol. 2024 Sep;96(9):e29871. doi: 10.1002/jmv.29871.

Abstract

The N121 site on the spike protein of SARS-CoV-2 is associated with heme and its metabolite, biliverdin, which can affect antibody binding. Both N121T and N121S substitutions have been observed in natural conditions and in a hamster model of dual infection with SARS-CoV-2 and Influenza A virus. Serum pseudotype neutralization assays against HIV-1 particles carrying wild-type, N121T, and N121S spikes with immune mouse and human sera revealed that N121T and N121S mutations had a greater impact on serum neutralization than biliverdin treatment. Although N121T and N121S substitutions are not currently major SARS-CoV-2 variants of concern, this study could provide fundamental information to prepare for potential future mutations at the N121 site of SARS-CoV-2.

Keywords: N121S; N121T; NTD; SARS‐CoV‐2; biliverdin; neutralizing.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19* / immunology
  • COVID-19* / virology
  • Humans
  • Mice
  • Mutation
  • Neutralization Tests*
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / immunology

Substances

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

Supplementary concepts

  • SARS-CoV-2 variants