Parida Pratap Kumar, Paul Dipak, Chakravorty Debamitra
Noor Enzymes Private Limited, 37-B, Darga Road, Kolkata 700 017, India.
Novel Techsciences (OPC) Private Limited, 37-B, Darga Road, 1st Floor, Kolkata 700 017, India.
Phytomed Plus. 2021 Feb;1(1):100002. doi: 10.1016/j.phyplu.2020.100002. Epub 2020 Nov 27.
Containing COVID-19 is still a global challenge. It has affected the "normal" world by targeting its economy and health sector. The effect is shifting of focus of research from life threatening diseases like cancer. Thus, we need to develop a medical solution at the earliest. The purpose of this present work was to understand the efficacy of 22 rationally screened phytochemicals from Indian medicinal plants obtained from our previous work, following drug-likeness properties, against 6 non-structural-proteins (NSP) from SARS-CoV-2.
100 ns molecular dynamics simulations were performed, and relative binding free energies were computed by MM/PBSA. Further, principal component analysis, dynamic cross correlation and hydrogen bond occupancy were analyzed to characterize protein-ligand interactions. Biological pathway enrichment analysis was also carried out to elucidate the therapeutic targets of the phytochemicals in comparison to SARS-CoV-2.
The potential binding modes and favourable molecular interaction profile of 9 phytochemicals, majorly from with lowest free binding energies, against the SARS-CoV-2 NSP targets were identified. It was understood that phytochemicals and 2 repurposed drugs with steroidal moieties in their chemical structures formed stable interactions with the NSPs. Additionally, human target pathway analysis for SARS-CoV-2 and phytochemicals showed that cytokine mediated pathway and phosphorylation pathways were with the most significant p-value.
To summarize this work, we suggest a global approach of targeting multiple proteins of SARS-CoV-2 with phytochemicals as a natural alternative therapy for COVID-19. We also suggest that these phytochemicals need to be tested experimentally to confirm their efficacy.
遏制新型冠状病毒肺炎（COVID-19）仍是一项全球挑战。它通过影响经济和卫生部门对“正常”世界产生了影响。这种影响使得研究重点从癌症等危及生命的疾病上转移。因此，我们需要尽早开发出一种医学解决方案。本研究的目的是了解从我们之前的工作中获得的、具有类药性的22种从印度药用植物中合理筛选出的植物化学物质对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的6种非结构蛋白（NSP）的疗效。
进行了100纳秒的分子动力学模拟，并通过MM/PBSA计算相对结合自由能。此外还分析了主成分分析、动态交叉相关性和氢键占有率，以表征蛋白质-配体相互作用。还进行了生物途径富集分析，以阐明与SARS-CoV-2相比植物化学物质的治疗靶点。
确定了9种主要来自[此处原文缺失相关信息]且具有最低自由结合能的植物化学物质与SARS-CoV-2 NSP靶点的潜在结合模式和有利的分子相互作用特征。据了解，植物化学物质和2种化学结构中含有甾体部分的重新利用药物与NSP形成了稳定的相互作用。此外，对SARS-CoV-2和植物化学物质的人类靶点途径分析表明，细胞因子介导的途径和磷酸化途径的p值最为显著。
总结这项工作，我们建议采用一种以植物化学物质靶向SARS-CoV-2多种蛋白质的全球方法，作为COVID-19的一种天然替代疗法。我们还建议对这些植物化学物质进行实验测试以确认其疗效。
