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.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, Spike protein, S-2P, cleavage, protein structure, hydrophobicity, isoelectric point, 【초록키워드】 Vaccine development, Infection, Transmission, viral entry, Spike protein, BNT162b2, Pfizer, Viral, mRNA, Viral variants, membrane fusion, function, Moderna, Pfizer/BioNTech, integration, Receptor binding, mRNA-1273 vaccine, domain, cell entry, foundation, candidate, SARS-2-S, human ACE2 receptor, vaccine candidates, prefusion, subunits, human cell, Cell, ENhance, produced, S1 and S2, approach, subsequent, events, variety, the spike protein, interact, translated, dissect, cleaved, build, 【제목키워드】 spike, Spike protein, function, Context,