Rajan Mariappan, Prabhakaran Selvakani, Prusty Jyoti Sankar, Chauhan Nagendra, Gupta Prashant, Kumar Awanish
Department of Natural Product Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India.
J Biomol Struct Dyn. 2023 Sep-Oct;41(15):7406-7420. doi: 10.1080/07391102.2022.2121758. Epub 2022 Sep 13.
The COVID-19 pandemic is spreading rapidly due to the outbreak of novel coronavirus SARS-CoV-2 across the globe. Anti-COVID-19 drugs are urgently required in this situation. In this regard, the discovery of promising new anti-COVID-19 moieties is expected from traditional medicine. The study is aimed to discover phytochemicals of having anti-COVID-19 activity via inhibiting main proteases of SARS-CoV-2. Main proteases (M) of SARS-CoV-2 serve as a protuberant target for anti-COVID-19 drug discovery because it is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription that makes it an attractive drug target. Recent studies indicated the utility of in the treatment of viral disorders like Dengue. Phytochemicals from were docked against SARS-CoV-2 main proteases (6LU7, 5R7Y, 5R7Z, 5R80, 5R81, 5R82) using the PyRx virtual screen tool and discovery studio visualizer. Further, molecular dynamics simulations were performed (for 100 ns) to see conformational stability for all complexes. Pharmacokinetic properties and drug-likeness prediction of selected phytoconstituents were also performed. Betulin, coclaurine, and quinic acid of were found promising with significant binding affinity to SARS-CoV-2 M in comparison to control. They have shown stable interactions with the amino acid residues present on the active site of most of the SARS-CoV-2 M and were found as promising anti-COVID-19 candidates. These compounds could be potential leads for the development of target-specific anti-COVID-19 therapeutics while ethnomedicinal uses of this herb could further needed for its detailed antiviral therapeutic exploration.Communicated by Ramaswamy H. Sarma.
由于新型冠状病毒SARS-CoV-2在全球范围内爆发，COVID-19大流行正在迅速蔓延。在这种情况下，迫切需要抗COVID-19药物。在这方面，有望从传统医学中发现新的抗COVID-19部分。该研究旨在通过抑制SARS-CoV-2的主要蛋白酶来发现具有抗COVID-19活性的植物化学物质。SARS-CoV-2的主要蛋白酶（M）是抗COVID-19药物发现的突出靶点，因为它是冠状病毒的关键酶，在介导病毒复制和转录中起关键作用，使其成为有吸引力的药物靶点。最近的研究表明其在治疗登革热等病毒疾病方面的效用。使用PyRx虚拟筛选工具和Discovery Studio可视化工具，将该植物的植物化学物质与SARS-CoV-2主要蛋白酶（6LU7、5R7Y、5R7Z、5R80、5R81、5R82）进行对接。此外，进行了分子动力学模拟（100纳秒）以观察所有复合物的构象稳定性。还对所选植物成分的药代动力学性质和药物相似性进行了预测。与对照相比，该植物的桦木醇、荷包牡丹碱和奎尼酸对SARS-CoV-2 M具有显著的结合亲和力，显示出有前景。它们与大多数SARS-CoV-2 M活性位点上的氨基酸残基表现出稳定的相互作用，被发现是有前景的抗COVID-19候选物。这些化合物可能是开发靶向特异性抗COVID-19疗法的潜在先导物，而该草药的民族药用用途可能需要进一步进行详细的抗病毒治疗探索。由Ramaswamy H. Sarma传达。
