Mohebbi Alireza, Askari Fatemeh Sana, Sammak Ali Salehnia, Ebrahimi Mohsen, Najafimemar Zahra
Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan 4934174515, Iran.
Student Research Committee, School of Medicine, Golestan University of Medical Sciences, Gorgan 4934174515, Iran.
Future Virol. 2021 May. doi: 10.2217/fvl-2020-0394.
Virus spike glycoprotein of SARS-CoV-2 is a good target for drug discovery. To examine the potential for druggability of spike protein for pharmacophore-based drug discovery and to investigate the binding affinity of natural products with SARS-CoV-2 spike protein. Druggable cavities were searched though CavityPlus. A pharmacophore was built and used for hit identification. Autodock Vina was used to evaluate the hits' affinities. 10 chemical derivatives were also made from the chemical backbone to optimize the lead compound. 10 druggable cavities were found within the glycoprotein spike. Only one cavity with the highest score at the binding site was selected for pharmacophore extraction. Hit identification resulted in the identification of 410 hits. This study provides a druggable region within viral glycoprotein and a candidate compound to block viral entry.
新型冠状病毒（SARS-CoV-2）的病毒刺突糖蛋白是药物研发的良好靶点。为了研究基于药效团的药物研发中刺突蛋白的成药潜力，并探究天然产物与SARS-CoV-2刺突蛋白的结合亲和力。通过CavityPlus搜索可成药腔。构建了一个药效团并用于命中化合物的识别。使用Autodock Vina评估命中化合物的亲和力。还从化学骨架制备了10种化学衍生物以优化先导化合物。在糖蛋白刺突内发现了10个可成药腔。仅选择结合位点处得分最高的一个腔进行药效团提取。命中化合物的识别产生了410个命中化合物。本研究提供了病毒糖蛋白内的一个可成药区域和一种阻断病毒进入的候选化合物。
