| SARS-CoV-2 M-pro inhibitors with antiviral activity in a transgenic mouse model |
| Qiao, JX; Li, YS; Zeng, R; Liu, FL; Luo, RH; Huang, C; Wang, YF; Zhang, J; Quan, BX; Shen, CJ; Mao, X; Liu, XL; Sun, WN; Yang, W; Ni, XC; Wang, K; Xu, L ; Duan, ZL; Zou, QC; Zhang, HL; Qu, W; Long, YHP; Li, MH; Yang, RC; Liu, XL; You, J; Zhou, YL; Yao, R; Li, WP; Liu, JM; Chen, P; Liu, Y; Lin, GF; Yang, X; Zou, J; Li, LL; Hu, YG; Lu, GW; Li, WM; Wei, YQ; Zheng, YT; Lei, J; Yang, SY
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| 2021
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| 发表期刊 | SCIENCE
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| ISSN | 0036-8075
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| 卷号 | 371期号:6536页码:1374-+ |
| 摘要 | The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (M-pro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing M-pro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 M-pro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of M-pro in complex with MI-23, one of themost potent compounds, revealed its interactionmode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment withMI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats. |
| 收录类别 | sci
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13801
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| 专题 | 科研部门_分子免疫药理学（郑永唐）
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推荐引用方式
GB/T 7714 |
Qiao, JX,Li, YS,Zeng, R,et al. SARS-CoV-2 M-pro inhibitors with antiviral activity in a transgenic mouse model[J]. SCIENCE,2021,371(6536):1374-+.
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| APA |
Qiao, JX.,Li, YS.,Zeng, R.,Liu, FL.,Luo, RH.,...&Yang, SY.(2021).SARS-CoV-2 M-pro inhibitors with antiviral activity in a transgenic mouse model.SCIENCE,371(6536),1374-+.
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| MLA |
Qiao, JX,et al."SARS-CoV-2 M-pro inhibitors with antiviral activity in a transgenic mouse model".SCIENCE 371.6536(2021):1374-+.
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