Screening of anti-SARS-CoV-2 small molecular compounds from traditional Chinese medicine based on molecular docking

ABSTRACT

Objective: Based on the targets of SARS-CoV-S/ACE2 complex and SARS-CoV-2 Mpro hydrolase, we screened the binding blockers of SARS-CoV-2-ACE2 and inhibitors of SARS-CoV-2 Mpro hydrolase from TCMSP database as precursors to guide the discovery of new drugs from small molecules of traditional Chinese medicine (TCM) against SARS-CoV-2. Methods: According to the literature reports, the active sites of the crystal structure model of SARS-CoV-S/ACE2 complex protein and SARS-CoV-2 Mpro hydrolase were determined, and the small molecular compounds from TCMSP database were virtually screened using LibDock molecular docking technology. The screening results were optimized by combining the LibDock Score with the interaction mode between the compounds and the targeting receptor protein, and then the small molecular compounds of TCM which have the potential activity of anti-SARS-CoV-2 were obtained. Results: ASP38, GLN42, GLN325, GLU329, TYR436, TYR491 on the binding surface of SARS-CoV-S/ACE2 complex protein and THR24, THR25, THR26, LEU27, ASN28, ASN119 in the structure of Mpro hydrolase were identified as the key amino acids for molecular docking. Twenty candidate SARS-CoV-2-ACE2 binding blockers which can form hydrogen bond with key amino acids were screened by molecular docking, and the docking effect of four components mainly from Gardeniae Fructus, Glycyrrhizae Radix Et Rhizoma, Sophorae Tonkinensis Radix Et Rhizoma and Daturae Flos with the targeting protein was better than others. Thirty-four candidate SARS-CoV-2 Mpro hydrolase inhibitors which can form hydrogen bond with key amino acids were also screened, and the docking effect of four components mainly from Zingiberis Rhizoma, Rhizoma Dioscoreae Bulbiferae, Cimicifugae Rhizoma and Capsella Bursa-pastoris with the targeting protein was better than others. Kanzonol E from Glycyrrhizae Radix Et Rhizoma and kryptogenin from Rhizoma Dioscoreae Bulbiferae could interact with the largest number of key amino acids or form the most hydrogen bonds with the targeting protein respectively, and had the best molecular docking effect. Conclusion: Four candidate SARS-CoV-2-ACE2 binding blockers and four candidate SARS-CoV-2 Mpro hydrolase inhibitors from TCM have the potential activity of anti-SARS-CoV-2, among which priority can be given to kanzonol E, a component of Glycyrrhizae Radix Et Rhizoma, and kryptogenin, a component of Rhizoma Dioscoreae Bulbiferae, for further discovery of anti-SARS-CoV-2 new drugs.