Screening of anti-SARS-CoV-2 leading compounds based on molecular docking technology

ABSTRACT

Objective To screen the novel small-molecule inhibitors against novel coronavirus(SARS-CoV-2), the binding protein combined spike protein of coronavirus(S protein) with angiotensin converting enzyme 2(ACE2) receptor was selected as the targets, based on compatibility-combination-TCM-compound database constructed by our group. Methods According to the virological and infection mechanisms of SARS-CoV-2, Q-Site Finder was used to identify the active sites on structural model of the binding protein combined S protein with ACE2 receptor, and molecular docking technology was employed to conduct the potential drug screening research from 4 kinds of 120 compounds such as betulinic acids, diosgenins, sterols, and podophyllotoxins by comparing the score value between the components of the same structure parent nucleusy. Results The active sites predicted by Q-site Finder were used as the key receptor residues for this molecular docking, and the structure parent nucleus of betulinic acid and diosgenin showed preferable binding ability, with 3beta-O-acetylated cholesterol(-13.1 kcal.mol-1), BH-11(-12.9 kcal.mol-1) and BH-12(-12.9 kcal.mol-1) as the top 3% compounds. Meanwhile, the structural parent nucleus of podophyllotoxin was not suitable for relevant research. Above results were verified by docking compounds with the higher absolute value of binding ability with 3 CLpro. Conclusion The structure parent nucleus of betulinic acid, diosgenin, as well as 3beta-O-acetylated cholesterol, BH-11 and BH-12 have the potential anti-SARS-CoV-2 effect, which can provide references for the subsequent new drug research and development against SARS-CoV-2.