Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on viral polyprotein processing, catalysed by the main proteinase (Mpro). The solution of the SARS-CoV-2 Mpro structure allowed the investigation of potential inhibitors. This work aims to provide first evidences of the applicability of commercially approved drugs to treat coronavirus disease-19 (COVID-19). We screened 4,334 compounds to found potential inhibitors of SARS-CoV-2 replication using an in silico approach. Our results evidenced the potential use of coagulation modifiers in COVID-19 treatment due to the structural similarity of SARS-CoV-2 Mpro and human coagulation factors thrombin and Factor Xa. Further in vitro and in vivo analysis are needed to corroborate these results.

严重急性呼吸综合征冠状病毒2（Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）的感染依赖于主蛋白酶（main proteinase, Mpro）催化的病毒多蛋白加工过程。SARS-CoV-2 Mpro的结构解析为潜在抑制剂的相关研究提供了支撑。本研究旨在为获批上市药物用于治疗新型冠状病毒肺炎（coronavirus disease-2019, COVID-19）提供初步依据。我们采用虚拟筛选（in silico）方法，对4334种化合物进行筛选，以期发现可抑制SARS-CoV-2复制的潜在抑制剂。研究结果表明，鉴于SARS-CoV-2 Mpro与人体凝血因子凝血酶（thrombin）及Xa因子（Factor Xa）存在结构相似性，凝血调节剂有望应用于COVID-19的治疗。不过，仍需开展进一步的体外（in vitro）与体内（in vivo）分析以佐证上述研究结论。