SARS-CoV-2 and SARS-CoV: Virtual screening of potential inhibitors targeting RNA-dependent RNA polymerase activity (NSP12)
SARS-CoV-2 and SARS-CoV: Virtual screening of potential inhibitors targeting RNA-dependent RNA polymerase activity (NSP12)
复制标题
SARS-CoV-2 和 SARS-CoV：针对 RNA 依赖性 RNA 聚合酶活性 (NSP12) 的潜在抑制剂的虚拟筛选
DOI：
10.1002/jmv.26222
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发表时间：
2020-07-09
影响因子：
12.7
通讯作者：
Yang, Tai
中科院分区：
文献类型：
--
作者：
Ruan, Zijing;Liu, Chao;Yang, Tai
自2003年严重急性呼吸系统综合症（SARS）爆发以来，冠状病毒对世界造成的危害不容小觑。最近，一种新型冠状病毒（严重急性呼吸综合征冠状病毒-2 [SARS-CoV-2]）最初于2019年在中国武汉市被发现引发人类严重呼吸道疾病，截至2020年6月21日，全球已有600多万人感染，并已被确认为国际关注的突发公共卫生事件。这种病毒已经传播到世界上200多个国家。然而，有效的药物尚未被正式许可或批准用于治疗SARS-Cov-2和SARS-Cov感染。SARS-CoV-2或SARS-CoV的NSP12-NSP7-NSP8复合体对病毒复制和转录至关重要，通常被认为是对抗病毒的潜在靶点。根据SARS-CoV-2的NSP12-NSP7- nsp8配合物（PDB ID: 7BW4）结构和SARS-CoV的NSP12-NSP7- nsp8配合物（PDB ID: 6NUR）结构，建立了NSP12-NSP7界面模型和NSP12-NSP8界面模型进行虚拟筛选。根据虚拟筛选和对接评分，选择8个化合物（Nilotinib、Saquinavir、Tipranavir、Lonafarnib、Tegobuvir、Olysio、Filibuvir和Cepharanthine）进行结合自由能计算。这8种化合物均能在晶体结构上与NSP12-NSP7-NSP8结合良好，为治疗和预防2019冠状病毒病和SARS提供候选药物。
Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the harm caused by coronaviruses to the world cannot be underestimated. Recently, a novel coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) initially found to trigger human severe respiratory illness in Wuhan City of China in 2019, has infected more than six million people worldwide by 21 June 2020, and which has been recognized as a public health emergency of international concern as well. And the virus has spread to more than 200 countries around the world. However, the effective drug has not yet been officially licensed or approved to treat SARS-Cov-2 and SARS-Cov infection. NSP12-NSP7-NSP8 complex of SARS-CoV-2 or SARS-CoV, essential for viral replication and transcription, is generally regarded as a potential target to fight against the virus. According to the NSP12-NSP7-NSP8 complex (PDB ID: 7BW4) structure of SARS-CoV-2 and the NSP12-NSP7-NSP8 complex (PDB ID: 6NUR) structure of SARS-CoV, NSP12-NSP7 interface model, and NSP12-NSP8 interface model were established for virtual screening in the present study. Eight compounds (Nilotinib, Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir, and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All eight compounds can combine well with NSP12-NSP7-NSP8 in the crystal structure, providing drug candidates for the treatment and prevention of coronavirus disease 2019 and SARS.