Department of Botany, Bioinformatics, and Climate Change Impacts Management, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India.
Department of Microbiology & Biotechnology, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India.
J Biomol Struct Dyn. 2022 Oct;40(17):7744-7761. doi: 10.1080/07391102.2021.1902393. Epub 2021 Mar 22.
The viral particle, SARS-CoV-2 is responsible for causing the epidemic of Coronavirus disease 2019 (COVID-19). To combat this situation, numerous strategies are being thought for either creating its antidote, vaccine, or agents that can prevent its infection. For enabling research on these strategies, several target proteins are identified where, Spike (S) protein is of great potential. S-protein interacts with human angiotensin-converting-enzyme-2 (ACE2) for entering the cell. S-protein is a large protein and a portion of it designated as a receptor-binding domain (RBD) is the key region that interacts with ACE2, following to which the viral membrane fuses with the alveolar membrane to enter the human cell. The hypothesis is to identify molecules from the pool of anticancer phytochemicals as a lead possessing the ability to interact and mask the amino acids of RBD, making them unavailable to form associations with ACE2. Such a molecule is termed as 'fusion inhibitor'. We hypothesized to identify fusion inhibitors from the NPACT library of anticancer phytochemicals. For this, all the molecules from the NPACT were screened using molecular docking, the five top hits (Theaflavin, Ginkgetin, Ursolic acid, Silymarin and Spirosolane) were analyzed for essential Pharmacophore features and their ADMET profiles were studied following to which the best two hits were further analyzed for their interaction with RBD using Molecular Dynamics (MD) simulation. Binding free energy calculations were performed using MM/GBSA, proving these phytochemicals containing anticancer properties to serve as fusion inhibitors.Communicated by Ramaswamy H. Sarma.
病毒粒子 SARS-CoV-2 是导致 2019 年冠状病毒病（COVID-19）流行的罪魁祸首。为了应对这种情况，人们正在思考许多策略，要么制造其解毒剂、疫苗，要么制造可以预防其感染的药物。为了能够进行这些策略的研究，已经确定了几个靶蛋白，其中刺突（S）蛋白具有很大的潜力。S 蛋白与人血管紧张素转换酶-2（ACE2）相互作用以进入细胞。S 蛋白是一种大型蛋白质，其一部分称为受体结合域（RBD）是与 ACE2 相互作用的关键区域，随后病毒膜与肺泡膜融合进入人体细胞。该假说旨在从抗癌植物化学物质库中识别出具有与 RBD 相互作用并掩盖其氨基酸的能力的分子，从而阻止它们与 ACE2 形成关联。这样的分子被称为“融合抑制剂”。我们假设从抗癌植物化学物质的 NPACT 库中识别出融合抑制剂。为此，使用分子对接筛选了 NPACT 中的所有分子，分析了前五个命中（茶黄素、银杏素、熊果酸、水飞蓟素和螺旋醇）的必需药效基团特征，并研究了它们的 ADMET 概况，随后对两个最佳命中进行了进一步分析，以了解它们与 RBD 的相互作用使用分子动力学（MD）模拟。使用 MM/GBSA 进行了结合自由能计算，证明这些具有抗癌特性的植物化学物质可以作为融合抑制剂。由 Ramaswamy H. Sarma 传达。
