This study elucidates for the first time that DBP functions as a broad-spectrum RBD inhibitor. It binds to the RBD-ACE2 interface, dependent on conserved residues Tyr453 and Tyr495, and acts primarily through steric hindrance to block the Spike-ACE2 interaction. Notably, DBP shares critical aromatic and ester groups with other active-site inhibitors. Structure-activity relationship analysis of its derivatives revealed that introducing additional hydrogen-bond acceptors significantly enhances inhibitory activity, providing a clear structure optimization strategy. While DBP has known toxicity, its antiviral potential may be harnessed through strategic delivery approaches or SAR-guided optimization to advance its development against SARS-CoV-2 variants.
Chen et al. (Tue,) studied this question.