Department of Botany, D.S.B Campus, Kumaun University, Nainital, Uttarakhand, India.
Department of Biotechnology, Bhimtal Campus, Kumaun University Uttarakhand, Bhimtal, Uttarakhand, India.
J Biomol Struct Dyn. 2022 Apr;40(6):2757-2768. doi: 10.1080/07391102.2020.1842806. Epub 2020 Nov 4.
The recent outbreak of SARS-CoV-2 disease, also known as COVID-19, has emerged as a pandemic. The unavailability of specific therapeutic drugs and vaccines urgently demands sincere efforts for drug discovery against COVID-19. The main protease (Mpro) of SARS-CoV-2 is a critical drug target as it plays an essential role in virus replication. Therefore for the identification of potential inhibitors of SARS-CoV-2 Mpro, we applied a structure-based virtual screening approach followed by molecular dynamics (MD) study. A library of 686 phytochemicals was subjected to virtual screening which resulted in 28 phytochemicals based on binding energy. These phytochemicals were further subjected to drug-likeness and toxicity analysis, which resulted in seven drug-like hits. Out of seven, five phytochemicals viz., Mpro-Dehydrtectol (-10.3 kcal/mol), Epsilon-viniferin (-8.6 kcal/mol), Peimisine (-8.6 kcal/mol), Gmelanone (-8.4 kcal/mol), and Isocolumbin (-8.4 kcal/mol) were non-toxic. Consequently, these phytochemicals are subjected to MD, post MD analysis, and MM/PBSA calculations. The results of 100 ns MD simulation, RMSF, SASA, Rg, and MM/PBSA show that Epsilon-viniferin (-29.240 kJ/mol), Mpro-Peimisine (-43.031 kJ/mol) and Gmelanone (-13.093 kJ/mol) form a stable complex with Mpro and could be used as potential inhibitors of SARS-CoV-2 Mpro. However, further investigation of these inhibitors against Mpro receptor of COVID-19 is needed to validate their candidacy for clinical trials. Communicated by Ramaswamy H. Sarma.
最近爆发的严重急性呼吸系统综合征冠状病毒 2 型疾病（SARS-CoV-2），又称 COVID-19，已成为一种大流行疾病。由于缺乏特定的治疗药物和疫苗，迫切需要真诚努力寻找针对 COVID-19 的药物。SARS-CoV-2 的主要蛋白酶（Mpro）是一个关键的药物靶点，因为它在病毒复制中起着至关重要的作用。因此，为了鉴定 SARS-CoV-2 Mpro 的潜在抑制剂，我们应用了基于结构的虚拟筛选方法，并结合分子动力学（MD）研究。对 686 种植物化学物质库进行了虚拟筛选，根据结合能得到了 28 种植物化学物质。这些植物化学物质进一步进行了药物相似性和毒性分析，得到了 7 种类药性命中。在这 7 种中，有 5 种植物化学物质，即 Mpro-Dehydrtectol（-10.3 kcal/mol）、Epsilon-viniferin（-8.6 kcal/mol）、Peimisine（-8.6 kcal/mol）、Gmelanone（-8.4 kcal/mol）和 Isocolumbin（-8.4 kcal/mol）是非毒性的。因此，这些植物化学物质被进一步进行 MD、MD 后分析和 MM/PBSA 计算。100 ns MD 模拟的结果、RMSF、SASA、Rg 和 MM/PBSA 表明，Epsilon-viniferin（-29.240 kcal/mol）、Mpro-Peimisine（-43.031 kcal/mol）和 Gmelanone（-13.093 kcal/mol）与 Mpro 形成稳定的复合物，可能作为 SARS-CoV-2 Mpro 的潜在抑制剂。然而，需要进一步研究这些抑制剂对 COVID-19 Mpro 受体的作用，以验证它们作为临床试验候选药物的资格。由 Ramaswamy H. Sarma 通讯。
