Recombinant SARS-CoV-2, S2 Protein

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded, positive-sense RNA virus that belongs to the Coronaviridae family 1. The SARS-CoV-2 genome, which shares 79.6% identity with SARS-CoV, encodes four essential structural proteins: the spike (S), envelope (E), membrane (M), and nucleocapsid protein (N) 2. The S protein is a transmembrane, homotrimeric, class I fusion glycoprotein that mediates viral attachment, fusion, and entry into host cells 3. Each ~180 kDa monomer contains two functional subunits, S1 (~700 a.a) and S2 (~600 a.a), that mediate viral attachment and membrane fusion, respectively. In both SARS-CoV and SARS-CoV-2, the receptor-binding domain (RBD) is at the C-terminus of S1 and binds to the angiotensin-converting enzyme 2 (ACE2) receptor on host cells 3-5. Following receptor binding, S1 destabilizes, and TMPRSS2 cleaves S2, which undergoes a pre- to post-fusion conformation transition, allowing for membrane fusion 4, 6. Unlike S1, S2 is conserved among coronaviruses, and the S2 of SARS-CoV-2 shares 88% sequence identity with SARS-CoV, suggesting that broadly neutralizing antibodies targeting S2 may cross-react with both viruses 4.