A non-RBM targeted RBD specific antibody neutralizes SARS-CoV-2 inducing S1 shedding

Biochem Biophys Res Commun. 2021 Sep 24:571:152-158. doi: 10.1016/j.bbrc.2021.07.062. Epub 2021 Jul 20.

Abstract

Potent neutralizing antibodies (Abs) have been proven with therapeutic efficacy for the intervention against SARS-CoV-2. Majority of these Abs function by directly interfering with the virus entry to host cells. Here, we identified a receptor binding domain (RBD) specific monoclonal Ab (mAb) 82A6 with efficient neutralizing potency against authentic SARS-CoV-2 virus. As most Abs targeting the non-receptor binding motif (RBM) region, 82A6 was incapable to block the RBD-ACE2 interaction. In particular, it actively promoted the S1 subunit shedding from the S protein, which may lead to effective reduction of intact SARS-CoV-2 viruses. Importantly, it could block potential syncytia formation associated with post-infectious cell surface expression of S proteins. Our study evidenced a RBD specific Ab with unique beneficial efficacy against SARS-CoV-2 infection, which might bring informative significance to understand the collective effects of neutralizing Abs elicited in COVID-19 patients.

Keywords: COVID-19; Neutralizing antibody; Receptor binding motif; S1 shedding; SARS-CoV-2; Syncytia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / therapeutic use*
  • Antibody Specificity
  • Binding Sites / immunology
  • COVID-19 / immunology
  • COVID-19 / therapy*
  • COVID-19 / virology
  • COVID-19 Serotherapy
  • Giant Cells / immunology
  • Giant Cells / virology
  • HEK293 Cells
  • Humans
  • Immunization, Passive
  • In Vitro Techniques
  • Protein Domains
  • Protein Subunits
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Virus Shedding

Substances

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