Severe acute respiratory syndrome coronavirus 2 spike glycoprotein (S protein) (S protein)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein is a large, trimeric class I fusion protein that mediates viral entry into host cells (UniProt: P0DTC2). It consists of two functional subunits: S1, which contains the receptor-binding domain (RBD) that attaches to the host cell receptor angiotensin-converting enzyme 2 (ACE2), and S2, which facilitates the fusion of the viral and host cell membranes (NCBI, 2020). As the primary surface antigen of the virus, the spike protein is the principal target for neutralizing antibodies, vaccines, and entry-inhibitor therapeutics (FDA, 2020). Tilorone, a synthetic small molecule originally developed as an interferon inducer, has been investigated in drug repurposing efforts for its potential to bind the spike protein and interfere with viral attachment or fusion processes (Ekins et al., 2020, "Tilorone, a Broad-Spectrum Antiviral for Emerging Viruses"). Therapeutic targeting of the spike protein faces significant challenges due to the high rate of mutation in the S gene, which leads to the emergence of variants of concern that can exhibit reduced susceptibility to existing monoclonal antibodies and vaccine-induced immunity (CDC, 2021). Consequently, monitoring spike protein mutations is essential for the ongoing development of effective COVID-19 countermeasures.

Other names

SARS-CoV-2 spike proteinSpike proteinS glycoproteinSurface glycoprotein

Inhibition of viral entry by blocking the interaction between the viral receptor-binding domain (RBD) and the host cell angiotensin-converting enzyme 2 (ACE2) receptor, or by preventing the conformational changes required for membrane fusion (NCBI, 2020; Ekins et al., 2020).