Neutralizing antibodies for the prevention and treatment of COVID-19

Cell Mol Immunol. 2021 Oct;18(10):2293-2306. doi: 10.1038/s41423-021-00752-2. Epub 2021 Sep 8.

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain (RBD) in the S1 subunit of the viral spike (S) protein. This event is followed by virus-cell membrane fusion mediated by the S2 subunit, which allows virus entry into the host cell. Therefore, the SARS-CoV-2 S protein is a key therapeutic target, and prevention and treatment of coronavirus disease 2019 (COVID-19) have focused on the development of neutralizing monoclonal antibodies (nAbs) that target this protein. In this review, we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date, with a focus on the N-terminal domain and RBD of the S protein. We also describe the roles that binding affinity, neutralizing activity, and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARS-CoV-2 variants. This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.

Keywords: COVID-19; Monoclonal antibodies; Neutralization; SARS-CoV-2; Spike protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / therapeutic use*
  • COVID-19 Drug Treatment*
  • Clinical Trials as Topic
  • Drug Approval
  • Drug Combinations
  • Humans
  • SARS-CoV-2 / chemistry*
  • Spike Glycoprotein, Coronavirus / chemistry*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Combinations
  • Spike Glycoprotein, Coronavirus
  • casirivimab and imdevimab drug combination
  • spike protein, SARS-CoV-2
  • bamlanivimab
  • etesevimab