Angiotensin-converting enzyme 2 (ACE2) – Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein interface (ACE2–SARS-CoV-2 S interface)

The Angiotensin-converting enzyme 2 (ACE2) – SARS-CoV-2 spike protein interface is the primary molecular gateway for the entry of the SARS-CoV-2 virus into human host cells [PubMed: 32142651]. 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 [UniProt: Q9BYF1]. This interaction is a prerequisite for viral attachment and subsequent membrane fusion, which allows the viral RNA to enter the cytoplasm [PubMed: 32225175]. As the critical first step of the infection cycle, this protein-protein interface is a major target for therapeutic development, including neutralizing monoclonal antibodies and vaccines [Nature: 583, 810–815]. Drugs targeting this interface typically function by competitively binding to the RBD, thereby sterically blocking its access to ACE2 [PubMed: 32514174]. However, the emergence of SARS-CoV-2 variants of concern (VOCs) with mutations in the RBD poses a significant challenge, as these changes can increase binding affinity or facilitate immune evasion [Science: 367, 1260-1263]. Consequently, ongoing research focuses on identifying conserved epitopes within the interface to develop more resilient, broad-spectrum therapeutics.

Other names

ACE2-Spike PPISARS-CoV-2 RBD-ACE2 interfaceSpike-ACE2 complexSARS-CoV-2 receptor binding domain-ACE2 interaction

Neutralization of viral particles by binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which sterically inhibits the interaction with the human ACE2 receptor and prevents viral entry into host cells [PubMed: 32514174].