Orfali Raha, Rateb Mostafa E, Hassan Hossam M, Alonazi Mona, Gomaa Mokhtar R, Mahrous Noura, GabAllah Mohamed, Kandeil Ahmed, Perveen Shagufta, Abdelmohsen Usama Ramadan, Sayed Ahmed M
Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia.
School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.
Antibiotics (Basel). 2021 Apr 11;10(4):420. doi: 10.3390/antibiotics10040420.
SARS CoV-2 is still considered a global health issue, and its threat keeps growing with the emergence of newly evolved strains. Despite the success in developing some vaccines as a protective measure, finding cost-effective treatments is urgent. Accordingly, we screened a number of phenolic natural compounds for their in vitro anti-SARS CoV-2 activity. We found sinapic acid (SA) selectively inhibited the viral replication in vitro with an half-maximal inhibitory concentration (IC) value of 2.69 µg/mL with significantly low cytotoxicity (CC = 189.3 µg/mL). Subsequently, we virtually screened all currently available molecular targets using a multistep in silico protocol to find out the most probable molecular target that mediates this compound's antiviral activity. As a result, the viral envelope protein (E-protein) was suggested as the most possible hit for SA. Further in-depth molecular dynamic simulation-based investigation revealed the essential structural features of SA antiviral activity and its binding mode with E-protein. The structural and experimental results presented in this study strongly recommend SA as a promising structural motif for anti-SARS CoV-2 agent development.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）仍然被视为一个全球健康问题，并且随着新进化毒株的出现，其威胁持续增加。尽管在开发一些疫苗作为防护措施方面取得了成功，但寻找具有成本效益的治疗方法迫在眉睫。因此，我们筛选了多种酚类天然化合物，以检测它们的体外抗SARS-CoV-2活性。我们发现芥子酸（SA）在体外选择性抑制病毒复制，其半数最大抑制浓度（IC）值为2.69μg/mL，细胞毒性显著较低（CC = 189.3μg/mL）。随后，我们使用多步骤计算机模拟方案对所有当前可用的分子靶点进行虚拟筛选，以找出介导该化合物抗病毒活性的最可能分子靶点。结果表明，病毒包膜蛋白（E蛋白）是SA最可能的作用靶点。基于分子动力学模拟的进一步深入研究揭示了SA抗病毒活性的基本结构特征及其与E蛋白的结合模式。本研究中呈现的结构和实验结果强烈推荐SA作为抗SARS-CoV-2药物开发的一个有前景的结构基序。
