The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens

Front Immunol. 2020 Oct 7:11:576622. doi: 10.3389/fimmu.2020.576622. eCollection 2020.


The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a grave threat to global public health and imposes a severe burden on the entire human society. Like other coronaviruses, the SARS-CoV-2 genome encodes spike (S) glycoproteins, which protrude from the surface of mature virions. The S glycoprotein plays essential roles in virus attachment, fusion and entry into the host cell. Surface location of the S glycoprotein renders it a direct target for host immune responses, making it the main target of neutralizing antibodies. In the light of its crucial roles in viral infection and adaptive immunity, the S protein is the focus of most vaccine strategies as well as therapeutic interventions. In this review, we highlight and describe the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development of the S protein-based vaccines as well as therapeutics.

Keywords: SARS-CoV-2; immunogen design; membrane fusion; neutralizing antibodies; receptor-binding domain; spike glycoprotein; structure; synthesis.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Betacoronavirus / immunology*
  • COVID-19
  • COVID-19 Vaccines
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control*
  • Humans
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Pandemics / prevention & control*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / prevention & control*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Vaccines / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines