SARS-CoV-2 Spike protein–Angiotensin-converting enzyme 2 interface (SARS-CoV-2 S–ACE2 interface)

The SARS-CoV-2 Spike protein–Angiotensin-converting enzyme 2 (ACE2) interface is the critical molecular contact point that mediates the entry of the SARS-CoV-2 virus into human host cells. The viral Spike (S) protein, specifically its receptor-binding domain (RBD), binds with high affinity to the extracellular peptidase domain of the human ACE2 receptor, which is widely expressed in the lungs, heart, and other tissues (UniProt P0DTC2, Q9BYF1). This binding event is a prerequisite for subsequent proteolytic cleavage of the Spike protein and fusion of the viral and host cell membranes. As the primary gateway for infection, this interface has been the central target for the development of neutralizing monoclonal antibodies and vaccines designed to block viral attachment (PubMed: 32275855). However, the interface is highly susceptible to mutations in the RBD, leading to the emergence of variants of concern that can evade existing therapeutic antibodies and vaccine-induced immunity (PubMed: 33688681). Therapeutic strategies focusing on this interface aim to provide immediate passive immunity or prevent severe disease progression in infected individuals.

Other names

SARS-CoV-2 S-ACE2 PPISpike-ACE2 binding interfaceRBD-ACE2 interfaceSARS-CoV-2 Spike-ACE2 complexSpike receptor-binding domain-ACE2 interface

Inhibition of the protein-protein interaction between the viral Spike protein receptor-binding domain (RBD) and the host ACE2 receptor, thereby preventing viral attachment and entry into host cells.