Binding and inhibitory effect of ravidasvir on 3CLpro of SARS-CoV-2: a molecular docking, molecular dynamics and MM/PBSA approach

被引:18
作者
Bera, Krishnendu [1 ,2 ]
机构
[1] Masaryk Univ, CEITEC MU, Kamenice 753-5, Brno 62500, Czech Republic
[2] Masaryk Univ, Fac Sci, Natl Ctr Biomol Res, Brno, Czech Republic
关键词
SARS-CoV-2; 3CL(pro); molecular docking; molecular dynamics simulation; principal component analysis; MM; PBSA;
D O I
10.1080/07391102.2021.1896388
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
Drug repurposing requires a limited resource, cost-effective and faster method to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, this in silico studies attempts to identify the drug-likeness properties of ravidasvir, an II/III phase clinical trial chronic hepatitis C drug against 3-Chymotrypsin-like protease (3CL(pro)) of SARS-CoV-2 to combat the ongoing coronavirus disease 2019 (COVID-19) pandemic. This protease is predominantly involved in virus replication cycle; hence it is considered as a potent drug target. The molecular docking results showed that ravidasvir was found to be potent inhibitors of 3CL(pro) with scoring function based binding energy is -26.7 kJ/mol. Further dynamic behaviour of apo form and complex form of ravidasvir with 3CL(pro) were studied using molecular dynamics (MD) simulations over 500 ns each, total 2 mu s time scale. The motion of the protein was studied using principal component analysis of the MD simulation trajectories. The binding free energy calculated using MM/PBSA method from the MD simulation trajectory was -190.3 +/- 70.2 kJ/mol and -106.0 +/- 26.7 kJ/mol for GROMOS96 54A7 and AMBER99SB-ILDN force field, respectively. This in silico studies suggesting ravidasvir might be a potential lead molecule against SARS-CoV-2 for further optimization and drug development to combat the life-threatening COVID-19 pandemic. Communicated by Ramaswamy H. Sarma
引用
收藏
页码:7303 / 7310
页数:8
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