Ao Shuang, Han Dan, Sun Lei, Wu Yanhong, Liu Shuang, Huang Yaojiang
Beijing Engineering Research Center of Food Environment and Public Health, Minzu University of China, Beijing, China.
College of Medicine, Minzu University of China, Beijing, China.
Front Genet. 2020 Nov 17;11:581668. doi: 10.3389/fgene.2020.581668. eCollection 2020.
RNA-dependent RNA polymerase (RdRp) is the key enzyme responsible for the SARS-CoV-2 replication process and catalyzes the synthesis of complementary minus strand RNA and genomic plus strand RNA, often recognized as good targets for antiviral drugs.
A systematic screening of existing antiviral compounds, family analysis, conserved domain analysis, three-dimensional structure modeling, drug virtual screening, and bioassays were performed to identify agents that potentially targeted RNA-dependent RNA polymerase of SARS-CoV-2.
Four thousand nine hundred and forty seven antiviral lead compounds were selected and evaluated by systematic screening. Of these, 359 agents were screened by family analysis and conserved domain analysis. They were further analyzed by three-dimensional structure modeling, virtual drug screening, and bioassays. The results identified 102 agents with potential for repurposing to target the RNA-dependent RNA polymerase of SARS-CoV-2.
This study identified 102 key agents with potential anti-SARS-CoV-2 RNA-dependent RNA polymerase function and prospects of rapid clinical application for the treatment of COVID-19.
RNA依赖性RNA聚合酶（RdRp）是负责严重急性呼吸综合征冠状病毒2（SARS-CoV-2）复制过程的关键酶，催化互补负链RNA和基因组正链RNA的合成，通常被认为是抗病毒药物的良好靶点。
对现有抗病毒化合物进行系统筛选、家族分析、保守结构域分析、三维结构建模、药物虚拟筛选和生物测定，以鉴定可能靶向SARS-CoV-2的RNA依赖性RNA聚合酶的药物。
通过系统筛选选择并评估了4947种抗病毒先导化合物。其中，359种药物通过家族分析和保守结构域分析进行筛选。它们通过三维结构建模、虚拟药物筛选和生物测定进一步分析。结果确定了102种具有重新用于靶向SARS-CoV-2的RNA依赖性RNA聚合酶潜力的药物。
本研究确定了102种具有潜在抗SARS-CoV-2 RNA依赖性RNA聚合酶功能以及快速临床应用于治疗2019冠状病毒病（COVID-19）前景的关键药物。
