Molecular biology of the SARs‐CoV‐2 spike protein: A review of current knowledge

Abstract

The global coronavirus disease 2019 (COVID‐19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has led to an unprecedented worldwide public health emergency. Despite the concerted efforts of the scientific field, by April 25, 2021, SARS‐CoV‐2 had spread to over 192 countries/regions, causing more than 146 million confirmed cases including 31 million deaths. For now, an established treatment for patients with COVID‐19 remains unavailable. The key to tackling this pandemic is to understand the mechanisms underlying its infectivity and pathogenicity. As a predominant focus, the coronavirus spike (S) protein is the key determinant of host range, infectivity, and pathogenesis. Thereby comprehensive understanding of the sophisticated structure of SARS‐CoV‐2 S protein may provide insights into possible intervention strategies to fight this ongoing global pandemic. Herein, we summarize the current knowledge of the molecular structural and functional features of SARS‐CoV‐2 S protein as well as recent updates on the cell entry mechanism of the SARS‐CoV‐2, paving the way for exploring more structure‐guided strategies against SARS‐CoV‐2.

Measurement of SARS-CoV-2 antigens in plasma of pediatric patients with acute COVID-19 or MIS-C using an ultrasensitive and quantitative immunoassay

“…Notably, they observed plasma N concentration ranges and association with disease severity similar to what we observed in children. The S-PLEX spike assay targets the receptor binding domain (RBD) within the S1 subunit; it can capture either the S1 domain (created by proteolytic cleavage at the S1-S2 junction [ 14 ]) or the full-length extracellular S1-S2 domain. Our spike assay had lower clinical sensitivity than our N assay in pediatric patients with acute COVID-19 (64% vs 89%), likely due to the consistently lower concentrations of S relative to N (approximately 22-fold).…”

The SARS-CoV-2 spike residues 616/644 and 1138/1169 delineate two antibody epitopes in COVID-19 mRNA COMINARTY vaccine (Pfizer/BioNTech)

“…The transmembrane S-protein spike homo-trimer at the virus surface mediates receptor binding through interaction with cell entry receptor ACE2 (14)(15)(16)(17)(18). The trimeric S protein contains the S1 and S2 subunits (10,11,14). The N-terminal S1 subunit which comprises the Receptor Binding Domain (RBD) is able to bind ACE2 and anti-RBD antibodies exert potent neutralizing activity against SARS-CoV-2 (10,11,13,14).…”

“…The N-terminal S1 subunit which comprises the Receptor Binding Domain (RBD) is able to bind ACE2 and anti-RBD antibodies exert potent neutralizing activity against SARS-CoV-2 (10,11,13,14). The C-terminal S2 subunit containing the fusion elements is responsible for viral membrane fusion with host-cell membranes (10,11,14). A furin-like cleavage site has been identified at the S1/S2 junction playing a major role in the pathogenesis of SARS-CoV-2 infection (18)(19)(20).…”

“…The structural spike protein playing a crucial role in eliciting the immune response during COVID-19 disease has been considered as the predominant viral antigen target for vaccine development (10)(11)(12)(13). The transmembrane S-protein spike homo-trimer at the virus surface mediates receptor binding through interaction with cell entry receptor ACE2 (14)(15)(16)(17)(18). The trimeric S protein contains the S1 and S2 subunits (10,11,14).…”

“…The trimeric S protein contains the S1 and S2 subunits (10,11,14). The N-terminal S1 subunit which comprises the Receptor Binding Domain (RBD) is able to bind ACE2 and anti-RBD antibodies exert potent neutralizing activity against SARS-CoV-2 (10,11,13,14). The C-terminal S2 subunit containing the fusion elements is responsible for viral membrane fusion with host-cell membranes (10,11,14).…”