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

The Severe acute respiratory syndrome coronavirus 2 spike glycoprotein (SARS-CoV-2 spike protein) is a large, trimeric class I fusion protein that decorates the surface of the SARS-CoV-2 virion and is essential for viral entry into host cells (UniProt: P0DTC2). It is composed of two functional subunits: the S1 subunit, which contains the receptor-binding domain (RBD) responsible for recognizing and attaching to the human angiotensin-converting enzyme 2 (ACE2) receptor, and the S2 subunit, which mediates the fusion of the viral and cellular membranes (PubMed: 32221306). The protein undergoes significant conformational changes, transitioning from a pre-fusion to a post-fusion state, a process triggered by host cell proteases like TMPRSS2 and furin (PubMed: 32142651). As the primary target of the humoral immune response, the spike protein is the focus of nearly all current COVID-19 vaccines and therapeutic monoclonal antibodies designed to neutralize the virus (NIH: COVID-19 Treatment Guidelines). However, the high rate of mutation in the spike protein, particularly in variants of concern like Omicron, poses a continuous challenge for vaccine efficacy and drug development due to potential immune evasion (PubMed: 35016195). Monitoring the structural integrity and antigenic profile of the spike protein remains a cornerstone of global public health efforts to manage the COVID-19 pandemic.

Other names

Spike glycoproteinS proteinSurface glycoproteinSARS-CoV-2 S proteinPeplomer protein

Neutralization of viral entry by binding to the receptor-binding domain (RBD) to block ACE2 interaction or by inhibiting the conformational changes required for membrane fusion (PubMed: 32221306, PubMed: 32142651).