Coronavirus disease 2019 (COVID-19) has caused more than 840,000 deaths as of 31 August 2020 in the whole world. The COVID-19 main protease (M^pro) has been validated as an attractive target for drug design. In this work, the binding mechanisms of five protease inhibitors (e.g., danoprevir, darunavir, ASC09, lopinavir and ritonavir) to COVID-19 M^pro were investigated. Based on the docking score, five protease inhibitors structures were selected for further evaluation. It is found that most of the selected drug molecules bind stably to the COVID-19 M^pro from the molecular dynamics simulation. Moreover, the MM/PBSA free energy calculations suggest that lopinavir with positive charge might be most active against COVID-19 M^pro.

截至 2020 年 8 月 31 日，2019 年冠状病毒病 (COVID-19) 已在全球造成超过 84 万人死亡。COVID-19 主要蛋白酶 (M ^pro ) 已被验证为药物设计的一个有吸引力的目标。在这项工作中，研究了五种蛋白酶抑制剂（例如达诺瑞韦、达芦那韦、ASC09、洛匹那韦和利托那韦）与COVID-19 M ^{pro的结合机制。}根据对接评分，选择五种蛋白酶抑制剂结构进行进一步评估。分子动力学模拟发现大多数选定的药物分子与COVID-19 M ^{pro稳定结合。}此外，MM/PBSA 自由能计算表明，带正电荷的洛匹那韦可能对 COVID-19 M ^pro最有效。