Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.
Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.
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阻断冠状病毒 SARS-CoV-2 刺突蛋白与其宿主细胞受体 ACE2 相互作用的潜在抑制剂
DOI：
10.1186/s12967-022-03501-9
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发表时间：
2022-07-14
影响因子：
7.4
通讯作者：
Qian, Chao-Nan
中科院分区：
文献类型：
--
作者：
Li, Changzhi;Zhou, Hongjuan;Guo, Lingling;Xie, Dehuan;He, Huiping;Zhang, Hong;Liu, Yixiu;Peng, Lixia;Zheng, Lisheng;Lu, Wenhua;Mei, Yan;Liu, Zhijie;Huang, Jie;Wang, Mingdian;Shu, Ditian;Ding, Liuyan;Lang, Yanhong;Luo, Feifei;Wang, Jing;Huang, Bijun;Huang, Peng;Gao, Song;Chen, Jindong;Qian, Chao-Nan
新冠肺炎疫情继续对人类健康和社会构成严重威胁。由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起的COVID-19大流行正在持续，对全球公共卫生和经济稳定构成严重威胁。鉴于形势的紧迫性，研究人员正试图重新利用现有药物来治疗COVID-19。我们首先基于均匀时间分辨荧光（HTRF）技术和冠状病毒刺突蛋白与其宿主受体ACE2的相互作用建立了抗冠状病毒药物筛选平台。利用该平台共筛选出两个化合物文库，共2864个分子。选择的候选化合物通过SARS-CoV-2_S假型慢病毒和ace2过表达细胞系统进行验证。分子对接分析了S蛋白与化合物的相互作用。我们鉴定出三种潜在的抗冠状病毒化合物：单宁酸（TA）、TS-1276（蒽醌）和TS-984（9-甲氧基canthin-6-one）。我们的体外验证实验表明，TS-984能强烈抑制冠状病毒S蛋白与人细胞ACE2受体的相互作用。单宁酸对S蛋白与ACE2的相互作用有中等抑制作用。该平台是一种快速、灵敏、特异、高通量的系统，可用于筛选大型化合物文库。TS-984是s蛋白与ACE2相互作用的有效阻断剂，有可能开发成有效的抗冠状病毒药物。在线版本包含补充材料，可在10.1186/s12967-022-03501-9获得。
The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug. The online version contains supplementary material available at 10.1186/s12967-022-03501-9.
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影响因子：
7.6
作者：
Ho TY;Wu SL;Chen JC;Li CC;Hsiang CY
通讯作者：
Hsiang CY
影响因子：
--
作者：
Hofmann-Winkler H;Moerer O;Alt-Epping S;Bräuer A;Büttner B;Müller M;Fricke T;Grundmann J;Harnisch LO;Heise D;Kernchen A;Pressler M;Stephani C;Tampe B;Kaul A;Gärtner S;Kramer S;Pöhlmann S;Winkler MS
通讯作者：
Winkler MS
影响因子：
158.5
作者：
Grein, J.;Ohmagari, N.;Flanigan, T.
通讯作者：
Flanigan, T.
影响因子：
7.6
作者：
Zhou Y;Vedantham P;Lu K;Agudelo J;Carrion R Jr;Nunneley JW;Barnard D;Pöhlmann S;McKerrow JH;Renslo AR;Simmons G
通讯作者：
Simmons G
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
通讯作者：
Olson, Arthur J.