Vijayakumar Mayakrishnan, Janani Balakarthikeyan, Kannappan Priya, Renganathan Senthil, Al-Ghamdi Sameer, Alsaidan Mohammed, Abdelaziz Mohamed A, Peer Mohideen Abubucker, Shahid Mohammad, Ramesh Thiyagarajan
Laboratory of Cell and Molecular Biology, Grassland and Forage Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan-si, Chungcheongnam-do 31000, Republic of Korea.
Department of Biochemistry, PSG College of Arts and Science (Autonomous), Affiliated to Bharathiar University, Coimbatore 641014, Tamil Nadu, India.
Saudi J Biol Sci. 2022 Jan;29(1):18-29. doi: 10.1016/j.sjbs.2021.10.060. Epub 2021 Oct 29.
The ongoing global outbreak of new corona virus (SARS-CoV-2) has been recognized as global public health concern since it causes high morbidity and mortality every day. Due to the rapid spreading and re-emerging, we need to find a potent drug against SARS-CoV-2. Synthetic drugs, such as hydroxychloroquine, remdisivir have paid more attention and the effects of these drugs are still under investigation, due to their severe side effects. Therefore, the aim of the present study was performed to identify the potential inhibitor against main protease SARS-CoV-2 6LU7.
In this study, RO5, ADME properties, molecular dynamic simulations and free binding energy prediction were mainly investigated.
The molecular docking study findings revealed that andrographolide had higher binding affinity among the selected natural diterpenoids compared to co-crystal native ligand inhibitor N3. The persistent inhibition of Ki for diterpenoids was analogous. Furthermore, the simulations of molecular dynamics and free binding energy findings have shown that andrographolide possesses a large amount of dynamic properties such as stability, flexibility and binding energy.
In conclusion, findings of the current study suggest that selected diterpenoids were predicted to be the significant phytonutrient-based inhibitor against SARS-CoV-2 6LU7 (M). However, preclinical and clinical trials are needed for the further scientific validation before use.
新型冠状病毒（SARS-CoV-2）在全球持续爆发，因其每日导致高发病率和死亡率，已成为全球公共卫生关注的焦点。由于其迅速传播和反复出现，我们需要找到一种有效的抗SARS-CoV-2药物。合成药物，如羟氯喹、瑞德西韦，因其严重的副作用，虽受到更多关注，但其效果仍在研究中。因此，本研究旨在确定针对主要蛋白酶SARS-CoV-2 6LU7的潜在抑制剂。
本研究主要考察RO5、ADME性质、分子动力学模拟和自由结合能预测。
分子对接研究结果显示，与共晶天然配体抑制剂N3相比，穿心莲内酯在所选天然二萜类化合物中具有更高的结合亲和力。二萜类化合物对Ki的持续抑制作用类似。此外，分子动力学模拟和自由结合能研究结果表明，穿心莲内酯具有大量的动力学性质，如稳定性、灵活性和结合能。
总之，本研究结果表明，所选二萜类化合物预计是针对SARS-CoV-2 6LU7（M）的重要的基于植物营养素的抑制剂。然而，在使用前还需要进行临床前和临床试验以进行进一步的科学验证。
