Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia.
Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Abbasia, Cairo 11566, Egypt.
Int J Mol Sci. 2022 Jun 21;23(13):6912. doi: 10.3390/ijms23136912.
In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (), Kahalalide E (), and Streptovaricin B () were determined as the most promising SARS-CoV-2 main protease (M) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with , the co-crystallized ligand of M (PDB ID: 6LU7), and favored thirty compounds. Subsequently, the fingerprint study performed with respect to resulted in the election of sixteen compounds (, , , , , , , , , , , , , , , and ). Then, results of molecular docking versus M PDB ID: 6LU7 favored eight compounds (, , , , , , , and ) based on their binding affinities. Then, in silico toxicity studies were performed for the promising compounds and revealed that all of them have good toxicity profiles. Finally, molecular dynamic (MD) simulation experiments were carried out for compounds , , and , which exhibited the best binding modes against M. MD tests revealed that luteoside C () has the greatest potential to inhibit SARS-CoV-2 main protease.
继我们先前针对 COVID-19 的工作之后，通过多步计算机模拟方法，从 310 种天然来源的抗病毒化合物中确定了三种天然化合物，即芦丁苷 C（）、卡拉哈利肽 E（）和链道霉素 B（），作为最有前途的 SARS-CoV-2 主要蛋白酶（M）抑制剂。首先，对 M 的共结晶配体（PDB ID：6LU7）与芦丁苷 C 进行分子结构相似性研究，并筛选出 30 种化合物。然后，对与 相关的指纹研究选出 16 种化合物（，，，，，，，，，，，，，，和）。然后，基于与 M（PDB ID：6LU7）的结合亲和力，分子对接结果筛选出 8 种化合物（，，，，，，和）。然后，对有前途的化合物进行计算机毒性研究，结果表明它们均具有良好的毒性特征。最后，对化合物 ，，和 进行分子动力学（MD）模拟实验，它们对 M 表现出最佳的结合模式。MD 测试表明，芦丁苷 C（）最有潜力抑制 SARS-CoV-2 主要蛋白酶。
