Rapid Structure-Based Screening Informs Potential Agents for Coronavirus Disease (COVID-19) Outbreak * Supported by the National Natural Science Foundation of China (Grant Nos. 11774279 and 11774280), the Fundamental Research Funds for the Central Universities of China (Grant Nos. xjj2017029 and xzy032020038), and the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2019JQ-603).
Rapid Structure-Based Screening Informs Potential Agents for Coronavirus Disease (COVID-19) Outbreak * Supported by the National Natural Science Foundation of China (Grant Nos. 11774279 and 11774280), the Fundamental Research Funds for the Central Universities of China (Grant Nos. xjj2017029 and xzy032020038), and the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2019JQ-603).
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基于结构的快速筛查为冠状病毒病 (COVID-19) 爆发的潜在病原体提供信息
DOI：
10.1088/0256-307x/37/5/058701
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发表时间：
2020-05
影响因子：
3.5
通讯作者：
中科院分区：
文献类型：
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由新型冠状病毒引起的2019冠状病毒病（COVID-19）在中国迅速蔓延。因此，迫切需要筛选和开发新的预防和治疗病毒感染的药物。基于快速结构的虚拟筛选用于评估目前的商业药物，结构包括人血管紧张素转换酶II （ACE2）和病毒主要蛋白酶、刺突蛋白、包膜蛋白、膜蛋白和核衣壳蛋白。我们的研究结果表明，已报道的药物阿比多尔、氯喹和瑞德西韦可能通过与ACE2、刺突和包膜蛋白的结合阻碍病毒粒子的进入和释放。由于结合模式相似，NHC （β-d-N4-hydroxycytidine）和Triazavirin也具有临床应用前景。主蛋白酶（3CLpro）可能是一个可行的药物设计靶点。针对3CL-pro的筛选结果显示，米托瓜酮、二甲双胍、盐酸双胍、没食子酸、咖啡酸、磺胺胍和乙酰半胱氨酸可能是新型冠状病毒肺炎的抑制剂，在临床治疗中具有潜在的应用价值。
Coronavirus Disease 2019 (COVID-19), caused by the novel coronavirus, has spread rapidly across China. Consequently, there is an urgent need to sort and develop novel agents for the prevention and treatment of viral infections. A rapid structure-based virtual screening is used for the evaluation of current commercial drugs, with structures of human angiotensin converting enzyme II (ACE2), and viral main protease, spike, envelope, membrane and nucleocapsid proteins. Our results reveal that the reported drugs Arbidol, Chloroquine and Remdesivir may hinder the entry and release of virions through the bindings with ACE2, spike and envelope proteins. Due to the similar binding patterns, NHC (β-d-N4-hydroxycytidine) and Triazavirin are also in prospects for clinical use. Main protease (3CLpro) is likely to be a feasible target of drug design. The screening results to target 3CL-pro reveal that Mitoguazone, Metformin, Biguanide Hydrochloride, Gallic acid, Caffeic acid, Sulfaguanidine and Acetylcysteine seem be possible inhibitors and have potential application in the clinical therapy of COVID-19.