Severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 S-RBD)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain (RBD) is a critical region of the S1 subunit of the viral spike glycoprotein (UniProt P0DTC2). Its primary biological function is to mediate high-affinity binding to the human angiotensin-converting enzyme 2 (ACE2) receptor, which serves as the primary entry point for the virus into host cells (PubMed: 32359621). Because the RBD-ACE2 interaction is essential for viral infection, the RBD is the principal target for neutralizing antibodies. Tixagevimab and cilgavimab are long-acting monoclonal antibodies that bind to distinct, non-overlapping epitopes on the RBD, providing a synergistic effect in neutralizing the virus and preventing infection (FDA: Evusheld Fact Sheet). These antibodies are used for pre-exposure prophylaxis and treatment of COVID-19, particularly in individuals who are immunocompromised or cannot be vaccinated. However, the rapid evolution of SARS-CoV-2 has led to frequent mutations within the RBD, such as those observed in various Omicron subvariants, which can significantly reduce or eliminate the neutralizing activity of these therapeutic antibodies (PubMed: 35016194).

Other names

SARS-CoV-2 RBDSpike protein RBDS1-RBDReceptor-binding domain of the SARS-CoV-2 spike glycoproteinTixagevimab-cilgavimab binding site

Neutralization of viral infectivity by binding to specific epitopes on the receptor-binding domain (RBD) of the spike protein, which sterically hinders the interaction with the human angiotensin-converting enzyme 2 (ACE2) receptor and prevents viral entry into host cells.