Identification of therapeutic drugs against COVID-19 through computational investigation on drug repurposing and structural modification

Yun, Yangfang; Song, Hengyi; Ji, Yin; Huo, Da; Han, Feng; Li, Fei; Jiang, Nan

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.