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针对 SARS-CoV-2 主蛋白酶 Mpro 的 COVID-19 治疗用凝血调节剂：一种计算机模拟方法。

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

机构信息

Laboratório de Proteômica Estrutural e Computacional, Instituto Carlos Chagas, Fundação Oswaldo Cruz-Fiocruz, Curitiba, PR, Brazil.

出版信息

Mem Inst Oswaldo Cruz. 2020;115:e200179. doi: 10.1590/0074-02760200179. Epub 2020 Jun 1.

DOI:10.1590/0074-02760200179
PMID:32490889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7265679/
Abstract

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.

摘要

严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染依赖于病毒多蛋白加工，由主要蛋白酶（Mpro）催化。SARS-CoV-2 Mpro 结构的解决方案允许研究潜在的抑制剂。这项工作旨在提供商业批准药物治疗冠状病毒病-19（COVID-19）的适用性的初步证据。我们使用计算机方法筛选了 4334 种化合物，以寻找 SARS-CoV-2 复制的潜在抑制剂。我们的结果证明了凝血调节剂在 COVID-19 治疗中的潜在用途，因为 SARS-CoV-2 Mpro 与人类凝血因子凝血酶和因子 Xa 具有结构相似性。需要进一步的体外和体内分析来证实这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0651/7265679/3140d66a24f8/1678-8060-mioc-115-e200179-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0651/7265679/f43a2c28dad6/1678-8060-mioc-115-e200179-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0651/7265679/3140d66a24f8/1678-8060-mioc-115-e200179-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0651/7265679/f43a2c28dad6/1678-8060-mioc-115-e200179-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0651/7265679/3140d66a24f8/1678-8060-mioc-115-e200179-gf2.jpg

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