Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design

• Published in: Viruses Vol. 13; no. 1; p. 109
• Main Author: Xia, Xuhua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-01-2021; MDPI
• Subjects: ACE2; Angiotensin-converting enzyme 2; Antibodies; Apoptosis; Binding sites; cleavage; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 - virology; COVID-19 Vaccines - genetics; COVID-19 Vaccines - immunology; Esophagus; Experiments; Homeostasis; Humans; Infections; Membrane Fusion; Molecular weight; mRNA; Mutation; Peptides; Protein Binding; Protein Domains; Protein Stability; Proteins; Receptors, Virus - metabolism; Review; S-2P; SARS-CoV-2; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Structure-function relationships; vaccine; Vaccine development; Vaccines; Virulence; Virus Internalization; Viruses; COVID-19; isoelectric point; protein structure; SARS-CoV-2; cleavage; hydrophobicity; vaccine; spike protein; S-2P
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13010109

The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech's BNT162b2 and Moderna's mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the mRNA is delivered into the human cell and translated. SARS-2-S is cleaved into S1 and S2 subunits, with S1 serving the function of receptor-binding and S2 serving the function of membrane fusion. Here, I dissect in detail the various domains of SARS-2-S and their functions discovered through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS-2-S works to achieve its function of mediating cell entry and subsequent cell-to-cell transmission. The integration of structure and function of SARS-2-S in this review should enhance our understanding of the dynamic processes involving receptor binding, multiple cleavage events, membrane fusion, viral entry, as well as the emergence of new viral variants. I highlighted the relevance of structural domains and dynamics to vaccine development, and discussed reasons for the spike protein to be frequently featured in the conspiracy theory claiming that SARS-CoV-2 is artificially created.