Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2

Li, C.; Zhou, H.; Guo, L.; Xie, D.; He, H.; Zhang, H.; Liu, Y.; Peng, L.; Zheng, L.; Lu, W.; Mei, Y.; Liu, Z.; Huang, J.; Wang, M.; Shu, D.; Ding, L.; Lang, Y.; Luo, F.; Wang, J.; Huang, B.; Huang, P.; Gao, S.; Chen, J.; Qian, C.-N.

doi:10.1101/2021.12.14.472545

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bioRxiv · 10.1101/2021.12.14.472545

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2

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Abstract

The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social and economic stability. In this study, we established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. This platform is a rapid, sensitive, specific, and high throughput system. With this platform, we screened two compound libraries of 2,864 molecules and 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. This data suggests that 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. SIGNIFICANCEThe 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 worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. In this present study, we screened two compound libraries of 2,864 molecules and identified a potent inhibitor (TS-984) for blocking the coronavirus S-protein and the human cell ACE2 receptor. TS-984 might have the potential to be developed into an effective anti-coronavirus drug for treating COVID-19.

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Li, C., Zhou, H., Guo, L., Xie, D., He, H., Zhang, H., Liu, Y., Peng, L., Zheng, L., Lu, W., Mei, Y., Liu, Z., Huang, J., Wang, M., Shu, D., Ding, L., Lang, Y., Luo, F., Wang, J., Huang, B., Huang, P., Gao, S., Chen, J., Qian, C.-N.. 2021-12-15. Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2. https://doi.org/10.1101/2021.12.14.472545

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