Khan Muhammad Tahir, Ali Arif, Wang Qiankun, Irfan Muhammad, Khan Abbas, Zeb Muhammad Tariq, Zhang Yu-Juan, Chinnasamy Sathishkumar, Wei Dong-Qing
Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Pakistan.
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, and Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education, Shanghai Jiao Tong University, China Shanghai.
J Biomol Struct Dyn. 2021 Jul;39(10):3627-3637. doi: 10.1080/07391102.2020.1769733. Epub 2020 Jun 1.
Sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA (ssRNA) virus, responsible for severe acute respiratory disease (COVID-19). A large number of natural compounds are under trial for screening compounds, possessing potential inhibitory effect against the viral infection. Keeping in view the importance of marine compounds in antiviral activity, we investigated the potency of some marine natural products to target SARS-CoV-2 main protease (M) (PDB ID 6MO3). The crystallographic structure of M in an apo form was retrieved from Protein Data Bank and marine compounds from PubChem. These structures were prepared for docking and the complex with good docking score was subjected to molecular dynamic (MD) simulations for a period of 100 ns. To measure the stability, flexibility, and average distance between the target and compounds, root mean square deviations (RMSD), root mean square fluctuation (RMSF), and the distance matrix were calculated. Among five marine compounds, C-1 (PubChem CID 11170714) exhibited good activity, interacting with the active site and surrounding residues, forming many hydrogen and hydrophobic interactions. The C-1 also attained a stable dynamic behavior, and the average distance between compound and target remains constant. In conclusion, marine natural compounds may be used as a potential inhibitor against SARS-CoV-2 for better management of COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种单链RNA（ssRNA）病毒，可导致严重急性呼吸疾病（COVID-19）。大量天然化合物正在进行筛选，以寻找对病毒感染具有潜在抑制作用的化合物。鉴于海洋化合物在抗病毒活性方面的重要性，我们研究了一些海洋天然产物针对SARS-CoV-2主要蛋白酶（M）（PDB ID 6MO3）的效力。从蛋白质数据库中检索了无配体形式的M的晶体结构，并从PubChem中获取了海洋化合物。对这些结构进行对接准备，对接分数良好的复合物进行了100纳秒的分子动力学（MD）模拟。为了测量目标与化合物之间的稳定性、灵活性和平均距离，计算了均方根偏差（RMSD）、均方根波动（RMSF）和距离矩阵。在五种海洋化合物中，C-1（PubChem CID 11170714）表现出良好的活性，与活性位点和周围残基相互作用，形成了许多氢键和疏水相互作用。C-1还表现出稳定的动力学行为，化合物与目标之间的平均距离保持恒定。总之，海洋天然化合物可作为SARS-CoV-2的潜在抑制剂，用于更好地管理COVID-19。
