State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
J Transl Med. 2022 Jul 14;20(1):314. doi: 10.1186/s12967-022-03501-9.
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.
SARS-CoV-2 的爆发继续对人类健康和社会造成严重威胁。由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的持续 COVID-19 大流行对全球公共卫生和经济稳定造成了严重威胁。鉴于形势的紧迫性，研究人员正在尝试重新利用现有的药物来治疗 COVID-19。
我们首先建立了基于均相时间分辨荧光（HTRF）技术和冠状病毒刺突蛋白与其宿主受体 ACE2 相互作用的抗冠状病毒药物筛选平台。用该平台筛选了两个 2864 种化合物的化合物库。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。分子对接用于分析 S 蛋白与化合物之间的相互作用。
我们确定了三种有潜力的抗冠状病毒化合物：鞣酸（TA）、TS-1276（蒽醌）和 TS-984（9-甲氧基卡亭-6-酮）。我们的体外验证实验表明，TS-984 强烈抑制冠状病毒 S 蛋白与人细胞 ACE2 受体的相互作用。此外，鞣酸对 S 蛋白与 ACE2 的相互作用表现出中等抑制作用。
该平台是一种快速、敏感、特异、高通量的系统，可用于筛选大型化合物库。TS-984 是 S 蛋白与 ACE2 相互作用的有效阻断剂，具有开发为有效抗冠状病毒药物的潜力。
