Screening for the novel coronavirus variant XBB.1.5 RBD inhibitors through molecular docking
Objective Virtual screening techniques was used to identify small-molecule inhibitors that can disrupt the interaction between the receptor-binding domain(RBD)protein on the S protein of the novel coronavirous XBB.1.5 variant and angiotensin-converting enzyme 2(ACE2),thereby impeding the novel coronavirus's recognition of the host.Methods We retrieved 486 387 ligand small molecules from the Mcule small molecule database.Subsequently,we conducted centroid-based molecular docking using the AutoDock Vina software,following the Jarvis-Patrick clustering.Results Key amino acid residues involved in the interaction between the XBB.1.5 RBD protein and ACE2 were identified.An in-depth analysis of the binding modes of five candidate small molecules with the XBB.1.5 RBD protein revealed that compound 1 formed π-π stacking and hydrogen bond interactions with TYR489 and SER490;compound 2 bond to TYR449,SER494,and TYR501 through hydrogen bonds and π-π stacking;compound 3 primarily formed hydrogen bonds with TYR451;compound 4 interacted with TYR427 via π-π stacking;and compound 5 formed π-cation stacking and hydrogen bonds with ARG381,GLN387,and ASN395 residues.These interactions disrupted the binding of the XBB.1.5 RBD to ACE2,thereby exerting an inhibitory effect.Additionally,the ADMET properties of the candidate compounds were simulated to predict their bioavailability,genotoxicity,and carcinogenicity,ultimately identifying potential inhibitor molecules.Conclusion Potential small molecule binders for the novel coronavious variant XBB.1.5 RBD protein are screened from the database.This aims are to hinder the binding between the S protein and ACE2,providing a reference for research and prescription screening in the fight against the novel coronavirus(SARS-CoV-2).
万方数据
维普
