The emergence and rapid spread of SARS-CoV-2 have caused a worldwide public health crisis. Designing small molecule inhibitors targeting SARS-CoV-2 S-RBD/ACE2 interaction is considered as a potential strategy for the prevention and treatment of SARS-CoV-2. But to date, only a few compounds have been reported as SARS-CoV-2 S-RBD/ACE2 interaction inhibitors. In this study, we described the virtual screening and experimental validation of two novel inhibitors (DC-RA016 and DC-RA052) against SARS-CoV-2 S-RBD/ACE2 interaction. The NanoBiT assays and surface plasmon resonance (SPR) assays demonstrated their capabilities of blocking SARS-CoV-2 S-RBD/ACE2 interaction and directly binding to both S-RBD and ACE2. Moreover, the pseudovirus assay revealed that these two compounds possessed significant antiviral activity (about 50% inhibition rate at maximum non-cytotoxic concentration). These results indicate that the compounds DC-RA016 and DC-RA052 are promising inhibitors against SARS-CoV-2 S-RBD/ACE2 interaction and deserve to be further developed.
【저자키워드】 SARS-CoV-2, Angiotensin-converting enzyme 2 (ACE2), Structure-based virtual screening, spike protein receptor-binding domain (S-RBD), protein-protein interaction (PPI) inhibitors, 【초록키워드】 Treatment, ACE2, Virtual screening, antiviral activity, public health crisis, SPR, inhibitors, Spread, pseudovirus, S-RBD, inhibitor, binding, Interaction, Concentration, experimental validation, Compound, described, caused, reported, demonstrated, small molecule inhibitor, 【제목키워드】 ACE2, Screening, S-RBD, identification, Potential,