Angiotensin-converting enzyme 2 (ACE2) receptor–SARS-CoV-2 spike protein interaction (ACE2–SARS-CoV-2 S interaction)

The interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is the primary mechanism for viral entry into host cells [PubMed: 32142651]. The spike protein, specifically its receptor-binding domain (RBD), recognizes and binds to the extracellular peptidase domain of ACE2 with high affinity [UniProt: Q9BYF1]. This binding event triggers a series of conformational changes and proteolytic processing by host enzymes like TMPRSS2, facilitating the fusion of the viral and host cell membranes [PubMed: 32225175]. Because this interaction is essential for the initiation of the COVID-19 infection cycle, it has become a central focus for therapeutic intervention [NIH: COVID-19 Treatment Guidelines]. Most neutralizing monoclonal antibodies and vaccines are designed to block this specific interface to prevent the virus from infecting respiratory and systemic tissues [PubMed: 32511530]. However, the rapid evolution of the spike protein leads to variants that can evade these treatments, presenting a significant challenge for long-term therapeutic efficacy [PubMed: 33585887].

Other names

ACE2-Spike interactionSARS-CoV-2 spike-ACE2 complexSpike-ACE2 binding interfaceSARS-CoV-2 entry receptor interaction

Neutralization of the viral spike protein receptor-binding domain (RBD) to competitively inhibit its binding to the host ACE2 receptor, thereby preventing viral attachment, membrane fusion, and subsequent cellular entry.