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

The interaction between human Angiotensin-converting enzyme 2 (hACE2) and the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein is the fundamental mechanism for viral entry into host cells [1]. The spike protein, a trimeric glycoprotein, utilizes its receptor-binding domain (RBD) to bind with high affinity to the extracellular peptidase domain of ACE2, which is expressed in various tissues including the lungs and heart [2][3]. This binding event triggers conformational changes and proteolytic processing by host enzymes like TMPRSS2, facilitating the fusion of viral and cellular membranes [4]. As the primary gateway for infection, this protein-protein interaction is a major focus for therapeutic development, particularly for neutralizing monoclonal antibodies and soluble receptor decoys [5]. These therapies aim to block the RBD-ACE2 interface, effectively neutralizing the virus before it can initiate replication [6]. However, the rapid evolution of the spike protein has led to variants of concern that can evade many existing treatments, posing a significant challenge for sustained therapeutic efficacy [7].

Other names

hACE2-Spike interactionSARS-CoV-2 entry receptor complexACE2-RBD bindingSpike-ACE2 complexSARS-CoV-2 S-ACE2 interaction

Neutralizing monoclonal antibodies and decoy receptors bind to the receptor-binding domain (RBD) of the viral spike protein, sterically blocking its ability to dock with the host cell's ACE2 receptor and thereby preventing viral attachment, membrane fusion, and subsequent infection.