Anti-SARS-CoV-2 Spike Protein S1 (NTD), mAb (rec.) (AB72-1-G09)

Coronaviruses (CoVs) are enveloped non-segmented positive-sense single-stranded RNA viruses and can infect respiratory, gastrointestinal, hepatic and central nervous system of human and many other wild animals. Recently, a new severe acute respiratory syndrome beta-coronavirus called SARS-CoV-2 (or 2019-nCoV) has emerged, which causes an epidemic of acute respiratory syndrome (called coronavirus human disease 2019 or COVID-19). SARS-CoV-2 shares 79.5% sequence identity with SARS-CoV and is 96.2% identical at the genome level to the bat coronavirus BatCoV RaTG133, suggesting it had originated in bats. SARS-CoV-2 contains 4 structural proteins, including Envelope (E), Membrane (M), Nucleocapsid (N) and Spike (S), which is a transmembrane protein, composed of two subunits S1 and S2. The S protein plays a key role in viral infection and pathogenesis. The S1 subunit contains the N-terminal domain (NTD) and a receptor binding domain (RBD), which binds to the cell surface receptor Angiotensin-Converting Enzyme 2 (ACE2) present at the surface of epithelial cells, causing mainly infection of human respiratory cells, whereas S2 harbors heptad repeat 1 (HR1) and HR2. The RBD domain first binds its receptor to form an RBD/ACE2 complex. This triggers conformational changes in the S protein, leading to membrane fusion mediated via HR1 and HR2 and consequently in viral entry into target cells. Antibodies targeting various regions of S protein have different mechanisms in inhibiting SARS-CoV-2 infection. For example, NTD-targeting antibodies bind the NTD to form an NTD/mAb complex, thereby preventing conformational changes in the S protein and blocking membrane fusion and viral entry. RBD-targeting antibodies form RBD/mAb or RBD/Nb complexes that inhibit binding of the RBD to ACE2, thereby preventing entry of SARS-CoV-2 into target cells. Protein function: [Spike protein S1]: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32221306, PubMed:32075877, PubMed:32155444). Binding to host NRP1 and NRP2 via C-terminal polybasic sequence enhances virion entry into host cell (PubMed:33082294, PubMed:33082293). This interaction may explain virus tropism of human olfactory epithelium cells, which express high level of NRP1 and NRP2 but low level of ACE2 (PubMed:33082293). The stalk domain of S contains three hinges, giving the head unexpected orientational freedom (PubMed:32817270). Uses human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Can be alternatively processed by host furin (PubMed:32362314). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. [The UniProt Consortium]