Yun Yangfang, Song Hengyi, Ji Yin, Huo Da, Han Feng, Li Fei, Jiang Nan
Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
The State Key Laboratory of Translational and Innovative Drug Development, Simcere Pharmaceutical Group, Nanjing, Jiangsu 210042, China.
J Biomed Res. 2020 Aug 31;34(6):458-469. doi: 10.7555/JBR.34.20200044.
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.
2019年冠状病毒病（COVID-19）在全球的流行促使人们迫切需要开发抗病毒疗法。与开发新药相比，药物重新利用可以显著降低成本、缩短时间并降低安全风险。鉴于冠状病毒利用刺突蛋白通过血管紧张素转换酶2（ACE2）侵入宿主细胞，因此我们研究是否有先前的抗病毒化合物可以阻断刺突蛋白与ACE2的相互作用并抑制病毒进入。分子对接和分子动力学模拟结果显示，在瑞德西韦、替诺福韦和洛匹那韦这三种化合物中，瑞德西韦对COVID-19表现出优于预期的抗病毒入侵潜力。此外，还发现瑞德西韦占据的表面积与抗病毒入侵潜力之间存在正相关。因此，通过酯键将N-苄基取代的二脒衍生物连接到瑞德西韦的羟基上，对其结构进行了修饰。结果发现，该化合物具有更高的抗病毒入侵潜力和更高的特异性。
