SARS-CoV-2 spike protein–Angiotensin-converting enzyme 2 (ACE2) protein–protein interface (SARS-CoV-2 S–ACE2 PPI)

The SARS-CoV-2 spike protein–Angiotensin-converting enzyme 2 (ACE2) protein–protein interface is the critical molecular gateway for the entry of the SARS-CoV-2 virus into human cells [1]. The viral spike protein, specifically its receptor-binding domain (RBD), recognizes and binds to the extracellular domain of the host's ACE2 receptor with high affinity [4]. This interaction triggers a series of conformational changes that facilitate viral-host membrane fusion or endocytosis, leading to infection [2]. As the primary site of viral attachment, this interface has become a focal point for therapeutic intervention, particularly for the development of neutralizing monoclonal antibodies and vaccines [3]. Drugs targeting this interface aim to block the physical interaction between the RBD and ACE2, thereby preventing the virus from infecting host cells [5]. However, the rapid evolution of the virus has led to mutations within this interface, resulting in variants of concern that can evade existing treatments [5]. Understanding the structural and biochemical nuances of this interface is essential for developing broad-spectrum antivirals and monitoring the efficacy of current therapies against emerging strains.

Other names

Spike-ACE2 interfaceRBD-ACE2 complexSARS-CoV-2 S-ACE2 interaction siteSpike-ACE2 protein-protein interaction

Inhibition of viral entry by competitively blocking the interaction between the SARS-CoV-2 spike protein receptor-binding domain (RBD) and the host cell Angiotensin-converting enzyme 2 (ACE2) receptor [1, 2].