Department of Biotechnology, Mepco Schlenk Engineering College, Sivakasi, Tamil Nadu, India.
Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Brno, Czech Republic.
J Biomol Struct Dyn. 2022 Apr;40(7):3155-3169. doi: 10.1080/07391102.2020.1845980. Epub 2020 Nov 17.
SARS-CoV-2 cause fatal infection in 213 countries accounting for the death of millions of people globally. In the present study, phytochemicals from spices were assessed for their ability to interact with SARS-CoV-2 M. Structure based virtual screening was performed with 146 phytochemicals from spices using Autodock Vina. Phytochemicals with binding energy ≥ -8.0 kcal/mol were selected to understand their interaction with M. Virtual screening was further validated by performing molecular docking to generate favorable docked poses and the participation of important amino acid residues. Molecular dynamics simulation for the docked poses was performed to study thermodynamic properties of the protein, ligand and protein-ligand complexes. The finding shows that cinnamtannin B2 and cyanin showed favorable binding affinity values with SARS-CoV-2 M. The results are comparable in terms of docked poses, important amino acid participation and thermodynamic properties with the standard control drugs remdesivir, benazepril and hydroxychloroquine diphosphate. Prime MM-GBSA was employed for end-point binding energy calculation. Binding to domain I and II of M were mediated through the OH, SH, NH and non-polar side chain of amino acids. Cinnamtannin B2 and cyanin binds to M with many sub sites within the active site with RMSD and RMSF within 4 Å. The results computed using Prime MM-GBSA show that cinnamtannin B2 (-68.54940214 kcal/mol) and cyanin (-62.1902835 kcal/mol) have better binding affinity in comparison to hydroxychloroquine diphosphate (-54.00912412 kcal/mol) and benazepril (-53.70242369 kcal/mol). The results provide a basis for exploiting cinnamtannin B2 and cyanin as a starting point potential candidate for the development of drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
SARS-CoV-2 在 213 个国家/地区引发致命感染，导致数百万人在全球范围内死亡。在本研究中，评估了来自香料的植物化学物质与 SARS-CoV-2 M 的相互作用能力。使用 Autodock Vina 对来自香料的 146 种植物化学物质进行了基于结构的虚拟筛选。选择结合能≥-8.0 kcal/mol 的植物化学物质来了解它们与 M 的相互作用。通过进行分子对接进一步验证虚拟筛选，以生成有利的对接构象，并参与重要的氨基酸残基。对对接构象进行分子动力学模拟，以研究蛋白质、配体和蛋白质-配体复合物的热力学性质。研究结果表明，肉桂单宁 B2 和矢车菊素与 SARS-CoV-2 M 具有良好的结合亲和力。在对接构象、重要氨基酸参与和热力学性质方面，结果与标准对照药物瑞德西韦、贝那普利和磷酸羟氯喹相当。采用 Prime MM-GBSA 进行终点结合能计算。肉桂单宁 B2 和矢车菊素通过 M 的 I 域和 II 域与 OH、SH、NH 和非极性侧链氨基酸结合。肉桂单宁 B2 和矢车菊素与 M 的活性部位内的许多亚基结合，RMSD 和 RMSF 在 4 Å 以内。使用 Prime MM-GBSA 计算的结果表明，肉桂单宁 B2（-68.54940214 kcal/mol）和矢车菊素（-62.1902835 kcal/mol）的结合亲和力优于磷酸羟氯喹（-54.00912412 kcal/mol）和贝那普利（-53.70242369 kcal/mol）。这些结果为开发针对 SARS-CoV-2 的药物提供了基础，可将肉桂单宁 B2 和矢车菊素作为潜在候选药物的起点。由 Ramaswamy H. Sarma 传达。
