Javaid Anum, Bibi Nousheen, Mahmood Malik Siddique, Batool Hina, Batool Sana, Hamid Arslan, Saleem Mahjabeen, Ashraf Naeem Mahmood, Afsar Tayyaba, Almajwal Ali, Razak Suhail
School of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan.
Department of Bioinformatics, Shaheed Benazir Bhutto Women University, Peshawar, Pakistan.
Curr Pharm Des. 2025;31(7):559-574. doi: 10.2174/0113816128315762240828052002.
New strains of SARS-CoV-2 are continually emerging worldwide. Recently, WHO warned of a severe new wave in Europe. Current vaccines cannot fully prevent reinfection in vaccinated individuals.
Given this issue, recent research focuses on new antiviral candidates with high efficacy and minimal side effects.
Screen natural compounds as inhibitors of M SARS-CoV-2 protein using molecular dynamics.
In this study, we have screened the potential of plant-based natural anti-viral compounds. A library of the 579 compounds was generated using currently available literature and online databases. All these compounds were screened based on their binding affinities as predicted by molecular docking analysis and compounds having binding affinity values ≤ -10 Kcal/mol were considered for analysis. Furthermore, from physicochemical assessment, drug-likeness initially nine compounds were identified as the antiviral targets for the selected viral proteins. After ADMET analysis and simulations, the compound 9064 with the lowest RMSD, Coul-SR interaction energy (-71.53 kJ/mol), and LJ-SR energy (-95.32 kJ/mol) was selected as the most stable drug candidate against COVID-19 main protease M.
The ΔG value, calculated using MMGBSA also revealed strong binding of the compound with M. The selected antiviral compound 9064 is an antioxidant flavonoid (Catechin or Cianidanol), which was previously known to have significant immunomodulatory, anti-inflammatory, and antioxidant properties.
Considering the limitations of currently available vaccines, our study may provide new insight into potential drugs that may prevent SARS-CoV-2 infection in humans.
新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）毒株在全球持续出现。最近，世界卫生组织警告欧洲将迎来新一轮严重疫情。目前的疫苗无法完全预防接种者再次感染。
鉴于这一问题，近期研究聚焦于高效且副作用最小的新型抗病毒候选药物。
利用分子动力学筛选天然化合物作为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）M蛋白的抑制剂。
在本研究中，我们筛选了植物源天然抗病毒化合物的潜力。利用现有文献和在线数据库生成了一个包含579种化合物的库。所有这些化合物均根据分子对接分析预测的结合亲和力进行筛选，结合亲和力值≤ -10千卡/摩尔的化合物被纳入分析。此外，通过理化评估，从药物相似性角度初步确定了9种化合物为所选病毒蛋白的抗病毒靶点。经过药物代谢动力学（ADMET）分析和模拟，选择均方根偏差（RMSD）最低、库仑-短程（Coul-SR）相互作用能（-71.53千焦/摩尔）和伦纳德-琼斯短程（LJ-SR）能（-95.32千焦/摩尔）的化合物9064作为针对2019冠状病毒病主要蛋白酶M最稳定的候选药物。
使用广义玻恩表面面积（MMGBSA）计算的自由能变化（ΔG）值也显示该化合物与M蛋白有强烈结合。所选的抗病毒化合物9064是一种抗氧化类黄酮（儿茶素或花青素醇），此前已知其具有显著的免疫调节、抗炎和抗氧化特性。
考虑到现有疫苗的局限性，我们的研究可能为预防人类感染SARS-CoV-2的潜在药物提供新的见解。
