Identification of Potential Inhibitors of 3CL Protease of SARS-CoV-2 From ZINC Database by Molecular Docking-Based Virtual Screening

被引:30
|
作者
Abdusalam, Ashraf Ahmed Ali [1 ]
Murugaiyah, Vikneswaran [2 ]
机构
[1] Sirte Univ, Fac Hlth Sci, Dept Pharmaceut Sci, Sirte, Libya
[2] Univ Sains Malaysia, Sch Pharmaceut Sci, Discipline Pharmacol, George Town, Malaysia
关键词
virtual screening; docking; ZINC database; COVID-19; SARS-CoV-2; 3CL protease; DRUG DISCOVERY; CRYSTAL-STRUCTURES; SARS; CORONAVIRUSES; STRATEGIES; INSIGHTS; UPDATE; MODEL;
D O I
10.3389/fmolb.2020.603037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The rapid outbreak of Coronavirus Disease 2019 (COVID-19) that was first identified in Wuhan, China is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The 3CL protease (3CLpro) is the main protease of the SARS-CoV-2, which is responsible for the viral replication and therefore considered as an attractive drug target since to date there is no specific and effective vaccine available against this virus. In this paper, we reported molecular docking-based virtual screening (VS) of 2000 compounds obtained from the ZINC database and 10 FDA-approved (antiviral and anti-malaria) on 3CLpro using AutoDock Vina to find potential inhibitors. The screening results showed that the top four compounds, namely ZINC32960814, ZINC12006217, ZINC03231196, and ZINC33173588 exhibited high affinity at the 3CLpro binding pocket. Their free energy of binding (FEB) were -12.3, -11.9, -11.7, and -11.2 kcal/mol while AutoDock Vina scores were -12.61, -12.32, -12.01, and -11.92 kcal/mol, respectively. These results were better than the co-crystallized ligand N3, whereby its FEB was -7.5 kcal/mol and FDA-approved drugs. Different but stable interactions were obtained between the four identified compounds with the catalytic dyad residues of the 3CLpro. In conclusion, novel 3CLpro inhibitors from the ZINC database were successfully identified using VS and molecular docking approach, fulfilling the Lipinski rule of five, and having low FEB and functional molecular interactions with the target protein. The findings suggests that the identified compounds may serve as potential leads that act as COVID-19 3CLpro inhibitors, worthy for further evaluation and development.
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页数:11
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