2019年冠状病毒病(COVID-19)在全球造成了令人震惊的情况,这是目前整个人口所面临的。无法控制的情况背后的主要原因之一是缺乏特定的治疗方法。在这样的条件下,对现有药物的药物再利用(即氯喹,洛匹那韦,等。)已经提出,但是各种临床和临床前研究表明这些药物的毒性和不良副作用。本研究使用分子对接和MD模拟研究,探索了Tinosporacordifolia(Giloy)的植物化学物质对SARSCoV-2可药用靶标(尖峰糖蛋白和Mpro蛋白)的抑制效力。ADMET,虚拟筛选,MD模拟,仿真后分析(RMSD,RMSF,Rg,SASA,PCA,进行了FES)和MM-PBSA计算,以预测植物化学物质对SARSCoV-2靶标的抑制作用。Tinospora化合物显示出比相应的参考更好的结合亲和力。它们与刺突蛋白的结合亲和力范围为-9.63至-5.68kcal/mole,与主要蛋白酶的结合亲和力范围为-10.27至-7.25kcal/mole。进一步的100ns详尽的模拟研究和MM-PBSA计算支持它们的有利和稳定的结合。这项工作确定了九种Tinospora化合物作为潜在的抑制剂。其中,发现7-去乙酰氧基-6,7-脱氢格杜宁同时抑制刺突(7NEG)和Mpro(7MGS和6LU7)蛋白,并且发现Columbin抑制选定的尖峰靶标(7NEG和7NX7)。在所有的分析中,这些化合物表现良好,证实了稳定的结合。因此确定的化合物,提倡作为潜在的抑制剂,可用于进一步的体外和体内实验验证,以确定其抗SARS-CoV-2的潜力。由RamaswamyH.Sarma沟通。
Coronavirus disease 2019 (COVID-19) caused appalling conditions over the globe, which is currently faced by the entire human population. One of the primary reasons behind the uncontrollable situation is the lack of specific therapeutics. In such conditions, drug repurposing of available drugs (viz. Chloroquine, Lopinavir, etc.) has been proposed, but various clinical and preclinical investigations indicated the toxicity and adverse side effects of these drugs. This
study explores the inhibition potency of phytochemicals from Tinospora cordifolia (Giloy) against SARS CoV-2 drugable targets (spike glycoprotein and Mpro proteins) using molecular docking and MD simulation studies. ADMET, virtual screening, MD simulation, postsimulation analysis (RMSD, RMSF, Rg, SASA, PCA, FES) and MM-PBSA calculations were carried out to predict the inhibition efficacy of the phytochemicals against SARS CoV-2 targets. Tinospora compounds showed better binding affinity than the corresponding reference. Their binding affinity ranges from -9.63 to -5.68 kcal/mole with spike protein and -10.27 to -7.25 kcal/mole with main protease. Further 100 ns exhaustive simulation studies and MM-PBSA calculations supported favorable and stable binding of them. This work identifies Nine Tinospora compounds as potential inhibitors. Among those, 7-desacetoxy-6,7-dehydrogedunin was found to inhibit both spike (7NEG) and Mpro (7MGS and 6LU7) proteins, and Columbin was found to inhibit selected spike targets (7NEG and 7NX7). In all the analyses, these compounds performed well and confirms the stable binding. Hence the identified compounds, advocated as potential inhibitors can be taken for further in vitro and in vivo experimental validation to determine their anti-SARS-CoV-2 potential.Communicated by Ramaswamy H. Sarma.