Muhtar Eldar, Wang Mengyang, Zhu Haimei
Beijing Area Major Laboratory of Peptide & Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, 100069, China.
Future Virol. 2021 Jul. doi: 10.2217/fvl-2021-0099. Epub 2021 Jul 20.
SARS-CoV-2 caused more than 3.8 million deaths according to the WHO. In this urgent circumstance, we aimed at screening out potential inhibitors targeting the main protease of SARS-CoV-2. An in-house carboline and quinoline database including carboline, quinoline and their derivatives was established. A virtual screening in carboline and quinoline database, 50 ns molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area calculations were carried out. The top 12 molecules were screened out preliminarily. The molecular mechanics Poisson-Boltzmann surface area ranking showed that p59_7m, p12_7e, p59_7k stood out with the lowest binding energies of -24.20, -17.98, -17.67 kcal/mol, respectively. The study provides powerful results that indicate the selected molecules are valuable for further evaluation as SARS-CoV-2 main protease inhibitors.
据世界卫生组织统计，新型冠状病毒肺炎已导致超过380万人死亡。在此紧急情况下，我们旨在筛选出针对新型冠状病毒主要蛋白酶的潜在抑制剂。建立了一个内部咔啉和喹啉数据库，其中包括咔啉、喹啉及其衍生物。在咔啉和喹啉数据库中进行了虚拟筛选、50纳秒分子动力学模拟以及分子力学泊松-玻尔兹曼表面积计算。初步筛选出了排名前12的分子。分子力学泊松-玻尔兹曼表面积排名显示，p59_7m、p12_7e、p59_7k表现突出，其结合能分别为-24.20、-17.98、-17.67千卡/摩尔，为最低。该研究提供了有力结果，表明所筛选出的分子作为新型冠状病毒主要蛋白酶抑制剂具有进一步评估的价值。
