SARS-CoV-2 spike receptor-binding domain–Angiotensin-converting enzyme 2 protein–protein interaction interface (SARS-CoV-2 RBD–ACE2 PPI)

The SARS-CoV-2 spike receptor-binding domain (RBD)–Angiotensin-converting enzyme 2 (ACE2) protein–protein interaction (PPI) interface is the primary gateway for the entry of the SARS-CoV-2 virus into human host cells (NIH, 2022; Nature Rev Mol Cell Biol, 2022). The viral spike protein's RBD binds with high affinity to the extracellular peptidase domain of the human ACE2 receptor, initiating a series of conformational changes that lead to membrane fusion and viral infection (NIH, 2020; Nature, 2020). This interface is a critical therapeutic target, as blocking this interaction can effectively neutralize the virus and prevent its spread (NIH, 2021). Numerous monoclonal antibodies, such as Bamlanivimab, Etesevimab, Casirivimab, and Imdevimab, have been developed to bind specifically to the RBD and sterically hinder its association with ACE2 (NIH, 2021; Cell Rep, 2021). Additionally, research into small-molecule inhibitors and recombinant soluble ACE2 aims to disrupt this PPI to treat COVID-19 (ResearchGate, 2021; NIH, 2022). However, the rapid evolution of the virus has led to mutations within the RBD, such as those found in the Delta and Omicron variants, which can enhance binding affinity or facilitate escape from existing neutralizing antibodies (Frontiers in Molecular Biosciences, 2022; bioRxiv, 2021).

Other names

SARS-CoV-2 Spike-ACE2 interfaceRBD-ACE2 complexACE2-interacting surfaceACE2ISSpike RBD-ACE2 interfaceSARS-CoV-2 RBD-hACE2 PPI

Inhibition of the protein-protein interaction between the SARS-CoV-2 spike protein receptor-binding domain (RBD) and the human Angiotensin-converting enzyme 2 (ACE2) receptor, thereby preventing viral attachment and subsequent entry into host cells (NIH, 2021; Nature, 2022).