Aminah Nanik Siti, Abdjan Muhammad Ikhlas, Wardana Andika Pramudya, Kristanti Alfinda Novi, Siswanto Imam, Rakhman Khusna Arif, Takaya Yoshiaki
Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga Surabaya 60115 Indonesia
Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga Indonesia.
RSC Adv. 2021 Dec 10;11(62):39455-39466. doi: 10.1039/d1ra07584e. eCollection 2021 Dec 6.
An investigation has been carried out on natural products from dolabellane derivatives to understand their potential in inhibiting the SARS-CoV-2 main protease (3CL) using an approach. Inhibition of the 3CL enzyme is a promising target in stopping the replication of the SARS-CoV-2 virus through inhibition of the subsite binding pocket. The redocking process aims to determine the 3CL active sites. The redocking requirement showed a good pose with an RMSD value of 1.39 Å. The combination of molecular docking and MD simulation shows the results of DD13 as a candidate which had a good binding affinity (kcal mol) to inhibit the 3CL enzyme activity. Prediction of binding free energy (kcal mol) of DD13 using the Molecular Mechanics-Poisson Boltzmann/Generalized Born Surface Area (MM-PB/GBSA) approach shows the results Δ : -52.33 ± 0.34 and Δ : -43.52 ± 0.42. The key residues responsible for the inhibition mechanism are Hie41, Ser46, Met49, Asn142, Cys145, Hie163, Met165, and Gln189. Additionally, pharmacokinetic prediction recommended that DD13 had promising criteria as a drug candidate. The results demonstrated in this study provide theoretical information to obtain a potential inhibitor against the SARS-CoV-2 main protease.
已对多拉贝烷衍生物的天然产物进行了一项研究，以了解它们使用一种方法抑制严重急性呼吸综合征冠状病毒2（SARS-CoV-2）主要蛋白酶（3CL）的潜力。抑制3CL酶是通过抑制亚位点结合口袋来阻止SARS-CoV-2病毒复制的一个有前景的靶点。重新对接过程旨在确定3CL的活性位点。重新对接要求显示出一个良好的构象，均方根偏差（RMSD）值为1.39 Å。分子对接和分子动力学（MD）模拟的结合显示，DD13作为一个候选物，对抑制3CL酶活性具有良好的结合亲和力（千卡/摩尔）。使用分子力学-泊松玻尔兹曼/广义玻恩表面积（MM-PB/GBSA）方法预测DD13的结合自由能（千卡/摩尔），结果显示Δ：-52.33±0.34和Δ：-43.52±0.42。负责抑制机制的关键残基是组氨酸41、丝氨酸46、甲硫氨酸49、天冬酰胺142、半胱氨酸145、组氨酸163、甲硫氨酸165和谷氨酰胺189。此外，药代动力学预测表明，DD13作为药物候选物具有有前景的标准。本研究中展示的结果提供了理论信息，以获得一种针对SARS-CoV-2主要蛋白酶的潜在抑制剂。
