Identification of therapeutic drugs against COVID-19 through computational investigation on drug repurposing and structural modification
Yangfang Yun1
Hengyi Song1
Yin Ji2
Da Huo1
Feng Han1
Fei Li1
Nan Jiang1
1.Key Laboratory of Cardiovascular&Cerebrovascular Medicine,School of Pharmacy,Nanjing Medical University,Naning,Jiangsu 211166,China2.The State Key Laboratory of Translational and Innovative Drug Development,Simcere Pharmaceutical Group,Nanjing,Jiangsu 210042,China
摘要：Global prevalence of coronavirus disease 2019 (COVID-19) calls for an urgent development of anti-viral regime. Compared with the development of new drugs, drug repurposing can significantly reduce the cost, time,and safety risks. Given the fact that coronavirus harnesses spike protein to invade host cells through angiotensin-converting enzyme 2 (ACE2), hence we see if any previous anti-virtual compounds can block spike-ACE2 interaction and inhibit the virus entry. The results of molecular docking and molecular dynamic simulations revealed that remdesivir exhibits better than expected anti-viral invasion potential against COVID-19 among the three types of compounds including remdesivir, tenofovir and lopinavir. In addition, a positive correlation between the surface area occupied by remdesivir and anti-viral invasion potential was also found. As such, the structure of remdesivir was modified by linking an N-benzyl substituted diamidine derivative to its hydroxyl group through an ester bond. It was found that this compound has a higher anti-viral invasion potential and greater specificity.
机标关键词：
分类号：R966(药理学)
论文发表日期：2020-11-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 458-469 )
英文信息