The Role of the SARS-CoV-2 S-Protein Glycosylation in the Interaction of SARS-CoV-2/ACE2 and Immunological Responses

Viral Immunol. 2021 Apr;34(3):165-173. doi: 10.1089/vim.2020.0174. Epub 2021 Feb 19.


The current pandemic is caused by the coronavirus disease 2019 (COVID-19), which is, in turn, induced by a novel coronavirus (SARS-CoV-2) that triggers an acute respiratory disease. In recent years, the emergence of SARS-CoV-2 is the third highly pathogenic event and large-scale epidemic affecting the human population. It follows the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. This novel SARS-CoV-2 employs the angiotensin-converting enzyme 2 (ACE2) receptor, like SARS-CoV, and spreads principally in the respiratory tract. The viral spike (S) protein of coronaviruses facilities the attachment to the cellular receptor, entrance, and membrane fusion. The S protein is a glycoprotein and is critical to elicit an immune response. Glycosylation is a biologically significant post-translational modification in virus surface proteins. These glycans play important roles in the viral life cycle, structure, immune evasion, and cell infection. However, it is necessary to search for new information about viral behavior and immunological host's response after SARS-CoV-2 infection. The present review discusses the implications of the CoV-2 S protein glycosylation in the SARS-CoV-2/ACE2 interaction and the immunological response. Elucidation of the glycan repertoire on the spike protein can propel research for the development of an appropriate vaccine.

Keywords: ACE2; N-glycosylation; O-glycosylation; S glycoprotein; SARS-CoV-2; immune response.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme 2 / physiology*
  • COVID-19 / immunology*
  • Glycosylation
  • Humans
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology*
  • Spike Glycoprotein, Coronavirus / physiology*


  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2