Abstract

The recent outbreak of the 2019 novel coronavirus disease (COVID-19) has been proved as a global threat. No particular drug or vaccine has not yet been discovered which may act specifically against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and causes COVID-19. For this highly infectious virus, 3CL-like main protease (3CL^pro) plays a key role in the virus life cycle and can be considered as a pivotal drug target. Structure-based virtual screening of DrugBank database resulted in 20 hits against 3CL^pro. Atomistic 100 ns molecular dynamics of five top hits and binding energy calculation analyses were performed for main protease-hit complexes. Among the top five hits, Nafarelin and Icatibant affirmed the binding energy (g_MMPBSA) of –712.94 kJ/mol and –851.74 kJ/mol, respectively. Based on binding energy and stability of protein-ligand complex; the present work reports these two drug-like hits against SARS-CoV-2 main protease.

Communicated by Ramaswamy H. Sarma

摘要

最近爆​​发的 2019 年新型冠状病毒病 (COVID-19) 已被证明是一种全球威胁。尚未发现可专门针对严重急性呼吸系统综合症冠状病毒-2 (SARS-CoV-2) 并导致 COVID-19 的特定药物或疫苗。对于这种传染性很强的病毒，3CL样主蛋白酶（3CL ^pro）在病毒生命周期中起着关键作用，可以被认为是关键的药物靶点。DrugBank 数据库的基于结构的虚拟筛选导致对 3CL ^{pro 的}20 次命中. 对主要蛋白酶命中复合物进行了五个顶级命中的原子 100 ns 分子动力学和结合能计算分析。在前五名中，Nafarelin 和 Icatibant 的结合能 (g_MMPBSA) 分别为 –712.94 kJ/mol 和 –851.74 kJ/mol。基于蛋白质-配体复合物的结合能和稳定性；目前的工作报告了这两种针对 SARS-CoV-2 主蛋白酶的类似药物的攻击。

由 Ramaswamy H. Sarma 交流