Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies

Viruses. 2021 Jan 19;13(1):134. doi: 10.3390/v13010134.

Abstract

Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike's receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.

Keywords: COVID-19; SARS-CoV-2; coronavirus; immunogen; neutralizing antibodies; spike.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / therapeutic use*
  • COVID-19 / therapy*
  • COVID-19 Serotherapy
  • Epitope Mapping
  • Epitopes / immunology
  • Humans
  • Immunization, Passive / methods
  • Middle East Respiratory Syndrome Coronavirus / immunology
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Severe Acute Respiratory Syndrome / therapy
  • Severe acute respiratory syndrome-related coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Viral Vaccines / immunology
  • Virus Internalization / drug effects

Substances

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