Bioinformatics Facility, Department of Botany, University of North Bengal, Siliguri, India.
Department of Biotechnology, Lovely Professional University, Phagwara, India.
J Biomol Struct Dyn. 2021 Aug;39(13):4774-4785. doi: 10.1080/07391102.2020.1780947. Epub 2020 Jun 19.
The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has rattled global public health, with researchers struggling to find specific therapeutic solutions. In this context, the present study employed an approach to assess the inhibitory potential of the phytochemicals obtained from GC-MS analysis of twelve species against the imperative spike protein, main protease enzyme M and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. An extensive molecular docking investigation of the phytocompounds at the active binding pockets of the viral proteins revealed promising inhibitory potential of the phytochemicals taraxerol, friedelin and stigmasterol. Decent physicochemical attributes of the compounds in accordance with Lipinski's rule of five and Veber's rule further established them as potential therapeutic candidates against SARS-CoV-2. Molecular mechanics-generalized Born surface area (MM-GBSA) binding free energy estimation revealed that taraxerol was the most promising candidate displaying the highest binding efficacy with all the concerned SARS-CoV-2 proteins included in the present analysis. Our observations were supported by robust molecular dynamics simulations of the complexes of the viral proteins with taraxerol for a timescale of 40 nanoseconds. It was striking to note that taraxerol exhibited better binding energy scores with the concerned viral proteins than the drugs that are specifically targeted against them. The present results promise to provide new avenues to further evaluate the potential of the phytocompound taraxerol and towards its successful deployment as a SARS-CoV-2 inhibitor and combat the catastrophic COVID-19.Communicated by Ramaswamy H. Sarma.
由新型冠状病毒 SARS-CoV-2 引起的 COVID-19 大流行扰乱了全球公共卫生，研究人员正在努力寻找特定的治疗方法。在这种情况下，本研究采用了一种方法来评估从十二种植物中通过 GC-MS 分析获得的植物化学物质对 SARS-CoV-2 的必需刺突蛋白、主蛋白酶 M 和 RNA 依赖性 RNA 聚合酶 (RdRp) 的抑制潜力。对植物化合物在病毒蛋白活性结合口袋中的广泛分子对接研究表明，植物化学物质 taraxerol、friedelin 和 stigmasterol 具有有希望的抑制潜力。根据 Lipinski 的五规则和 Veber 的规则，这些化合物具有良好的物理化学特性，进一步确立了它们作为针对 SARS-CoV-2 的潜在治疗候选物。分子力学-广义 Born 表面积 (MM-GBSA) 结合自由能估算表明，taraxerol 是最有前途的候选物，与本分析中包含的所有相关 SARS-CoV-2 蛋白均显示出最高的结合效力。我们的观察结果得到了病毒蛋白与 taraxerol 复合物的稳健分子动力学模拟的支持，模拟时间长达 40 纳秒。值得注意的是，taraxerol 与相关病毒蛋白的结合能评分优于专门针对它们的药物。本研究结果有望为进一步评估植物化合物 taraxerol 的潜力提供新途径，并将其成功用作 SARS-CoV-2 抑制剂，以应对灾难性的 COVID-19。由 Ramaswamy H. Sarma 传达。
