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

The SARS-CoV-2 Spike glycoprotein – Angiotensin-converting enzyme 2 (ACE2) interface is the primary molecular contact point between the virus and the host cell, facilitating viral attachment and subsequent entry [1, 7]. The interaction occurs between the receptor-binding domain (RBD) of the viral Spike (S) protein and the peptidase domain of the human ACE2 receptor, which is widely expressed in the lungs, heart, and other tissues [4, 12]. This high-affinity protein-protein interaction triggers conformational changes in the Spike protein that lead to membrane fusion and the release of the viral genome into the host cell [7, 14]. As the essential first step of infection, this interface is the principal target for most COVID-19 vaccines and therapeutic monoclonal antibodies, which function by sterically blocking the RBD-ACE2 engagement [2, 20]. However, the emergence of viral variants with mutations at this interface poses a significant challenge, as these changes can enhance binding affinity or enable the virus to evade existing immune responses and therapeutic agents [3, 15]. Ongoing research also explores soluble ACE2 decoys and small-molecule inhibitors to provide broader protection against evolving viral strains [9, 16].

Other names

RBD-ACE2 interfaceSpike-ACE2 binding siteSARS-CoV-2 RBD-ACE2 complexACE2-interacting surfaceACE2IS

Competitive inhibition of the protein-protein interaction between the viral receptor-binding domain (RBD) and the host ACE2 receptor, leading to viral neutralization and prevention of cellular entry [2, 4, 9].