Structure-function relations of the SARS-CoV-2 spike protein and impact of mutations in the variants of concern
- 21 June 2021
- journal article
- research article
- Published by Cellule MathDoc/CEDRAM in Comptes Rendus Biologies
- Vol. 344 (1), 77-110
- https://doi.org/10.5802/crbiol.53
Abstract
This review covers the main features of the severe acquired respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, its interaction with the main entry receptor, the human angiotensin converting enzyme 2 (ACE2), and the subsequent membrane fusion step. The focus is on the structural organization of these proteins and mechanistic aspects of their interactions that lead to cytoplasmic release of the viral genome. The most potently neutralizing antibodies against SARS-CoV-2 were shown to interfere with the spike/ACE2 interaction. I thus also review the location and the potential impact of mutations in the spike protein observed in the variants of concern that emerged concomitantly with acquired immunity in the population after one year of virus circulation. Understanding how these interactions affect the spike/ACE2 interactions and the subsequent spike-protein-induced membrane fusion reaction is important to stay one step ahead of the virus evolution and develop efficient countermeasures.Keywords
This publication has 119 references indexed in Scilit:
- Structural basis for multifunctional roles of mammalian aminopeptidase NProceedings of the National Academy of Sciences of the United States of America, 2012
- The solute carrier 6 family of transportersBritish Journal of Pharmacology, 2012
- Recent advances involving the renin–angiotensin systemExperimental Cell Research, 2012
- A redox switch in angiotensinogen modulates angiotensin releaseNature, 2010
- Viral membrane fusionNature Structural & Molecular Biology, 2008
- ACE2 X-Ray Structures Reveal a Large Hinge-bending Motion Important for Inhibitor Binding and CatalysisOnline Journal of Public Health Informatics, 2004
- A Human Homolog of Angiotensin-converting EnzymeOnline Journal of Public Health Informatics, 2000
- Direct Association of Adenosine Deaminase with a T Cell Activation Antigen, CD26Science, 1993
- Aminopeptidase N is a major receptor for the enteropathogenic coronavirus TGEVNature, 1992
- THE PREPARATION AND FUNCTION OF THE HYPERTENSIN-CONVERTING ENZYMEThe Journal of Experimental Medicine, 1956