Department of Pharmaceutical Chemistry, College of Science, Charmo University, Chamchamal, Sulaimani, Iraq.
Department of BioMedical Science, College of Science, Komar University of Science and Technology, Sulaimani, Iraq.
J Biomol Struct Dyn. 2024 May;42(8):4234-4248. doi: 10.1080/07391102.2023.2220040. Epub 2023 Jun 22.
The largest threat to civilization since the Second World War is the spread of the new coronavirus disease (COVID-19). Therefore, there is an urgent need for innovative therapeutic medicines to treat COVID-19. Reusing bio-actives is a workable and efficient strategy in the battle against new epidemics because the process of developing new drugs is time-consuming. This research aimed to identify which herbal remedies had the highest affinity for the receptor and assess a variety of them for potential targets to suppress the SARS-CoV-2 M. The use of AutoDock Vina for structure-based virtual screening was done first due to the importance of protein interactions in the development of drugs. Molecular docking was used in the comparative study to assess 89 different chemicals from medicinal herbs. To anticipate their effectiveness against the primary protease of SARS-CoV-2, more analysis was done on the ADMET profile, drug-likeness, and Lipinski's rule of five. The next step involved three replicas of 100 ns-long molecular dynamics simulations on the potential candidates, which were preceded by calculations of the binding free energy of MM-GBSA. The outcomes showed that Achyrodimer A, Cinchonain Ib, Symphonone F, and Lupeol acetate all performed well and had the highest 6LU7 binding affinities. Using RMSD, RMSF, and protein-ligand interactions, the stability of the protein-ligand complex was assessed. The studies indicate that bioactive substances obtained from herbal medicines may function as a COVID-19 therapeutic agent, necessitating additional wet lab research to confirm their therapeutic potential, efficacy, and pharmacological capacity against the condition.Communicated by Ramaswamy H. Sarma.
自第二次世界大战以来，对文明的最大威胁是新型冠状病毒病（COVID-19）的传播。因此，迫切需要创新的治疗药物来治疗 COVID-19。再利用生物活性物质是应对新流行病的可行且有效的策略，因为开发新药的过程非常耗时。本研究旨在确定哪些草药具有最高的受体亲和力，并评估多种草药作为抑制 SARS-CoV-2 M 的潜在靶点。由于蛋白质相互作用在药物开发中的重要性，首先使用 AutoDock Vina 进行基于结构的虚拟筛选。在比较研究中使用分子对接来评估来自草药的 89 种不同化学物质。为了预测它们对 SARS-CoV-2 主要蛋白酶的有效性，对 ADMET 概况、药物相似性和 Lipinski 的五规则进行了更多分析。下一步是对潜在候选物进行三组长达 100 ns 的分子动力学模拟，在此之前，计算 MM-GBSA 的结合自由能。结果表明，Achyrodimer A、Cinchonain Ib、Symphonone F 和乙酸羽扇醇都表现良好，具有最高的 6LU7 结合亲和力。使用 RMSD、RMSF 和蛋白质-配体相互作用评估蛋白质-配体复合物的稳定性。这些研究表明，草药中的生物活性物质可能作为 COVID-19 治疗剂发挥作用，需要进行更多的湿实验室研究来确认其治疗潜力、疗效和对该疾病的药理学能力。由 Ramaswamy H. Sarma 传达。
