Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein S1 subunit (SARS-CoV-2 S1) (SARS-CoV-2 S1)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein S1 subunit is the critical surface component of the virus responsible for initiating host cell infection by binding to the human angiotensin-converting enzyme 2 (ACE2) receptor (UniProt P0DTC2). It contains the receptor-binding domain (RBD) and the N-terminal domain (NTD), which are the primary targets for neutralizing antibodies elicited by infection or vaccination. The original (Wuhan-Hu-1) S1 sequence formed the basis for initial therapeutic development, but the emergence of the Omicron BA.4 and BA.5 lineages introduced specific mutations (such as L452R and F486V) that significantly enhance ACE2 binding affinity and facilitate escape from previous immune responses (Cao et al., Nature 2022). Consequently, bivalent vaccines were developed to include both the original and BA.4/BA.5 S1 sequences to broaden the spectrum of neutralizing antibodies (FDA, 2022). Therapeutic monoclonal antibodies target the S1 subunit to block viral entry, though their clinical utility is frequently challenged by the protein's high rate of mutational plasticity. Understanding the structural dynamics of the S1 subunit across these lineages is essential for the design of next-generation COVID-19 biologics and vaccines (Wang et al., Cell 2022). The S1 subunit also plays a role in triggering the host immune response, making it the central focus of global immunization efforts. Monitoring the evolution of this subunit is vital for predicting the efficacy of existing countermeasures.

Other names

S1 subunitSpike protein S1SARS-CoV-2 S1 proteinReceptor-binding domain-containing subunitSARS-CoV-2 S1 (Original/Omicron BA.4/BA.5)

Neutralization of viral entry by competitively inhibiting the binding of the S1 receptor-binding domain (RBD) to the host angiotensin-converting enzyme 2 (ACE2) receptor (Wang et al., Nature 2022).