Structural Basis of Main Proteases of Coronavirus Bound to Bofutrelvir
文献类型：期刊论文
| 作者 | Wang, Wei-wei5; Zeng, Pei4; Liu, Tongchao3; Zhou, Xue-lan2; Lin, Cheng1; Guo, Li1; Wang, Qi-sheng5; Li, Jian4 |
| 刊名 | JOURNAL OF MOLECULAR BIOLOGY
 |
| 出版日期 | 2024-11-15 |
| 卷号 | 436期号:22页码:16 |
| 关键词 | SARS-CoV-2 Coronavirus Main protease Mutants Inhibitor |
| ISSN号 | 0022-2836 |
| DOI | 10.1016/j.jmb.2024.168784 |
| 通讯作者 | Wang, Qi-sheng(wangqs@sari.ac.cn) ; Li, Jian(rmsl_2040@163.com) |
| 英文摘要 | Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (M-pro) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 M-pro, demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the M-pro of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the M-pro of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 M-pro mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to M(pro)s from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the M-pro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future. |
| WOS关键词 | SARS |
| 资助项目 | National Natural Science Foundation of China[82204187] ; National Natural Science Foundation of China[82360701] ; Jiangxi natural science foundation for distinguished young scholar[20212ACB216001] ; Gannan Medical University[QD201910] ; Jiangxi key research and development program[20203BBG73063] ; Jiangxi Double Thousand Plan[jxsq2019101064] ; Natural Science Foundation of Shanghai[21ZR1471800] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001316995500001 |
| 出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313424]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Qi-sheng; Li, Jian |
| 作者单位 | 1.Jiangxi Jmerry Biopharmaceut Co Ltd, Ganzhou 341000, Peoples R China 2.Shenzhen Crystalo Biopharmaceut Co Ltd, Shenzhen 518118, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 4.Gannan Med Univ, Sch Pharm, Jiangxi Prov Key Lab Pharmacol Tradit Chinese Med, Ganzhou 341000, Peoples R China 5.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai 201204, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Wei-wei,Zeng, Pei,Liu, Tongchao,et al. Structural Basis of Main Proteases of Coronavirus Bound to Bofutrelvir[J]. JOURNAL OF MOLECULAR BIOLOGY,2024,436(22):16. |
| APA | Wang, Wei-wei.,Zeng, Pei.,Liu, Tongchao.,Zhou, Xue-lan.,Lin, Cheng.,...&Li, Jian.(2024).Structural Basis of Main Proteases of Coronavirus Bound to Bofutrelvir.JOURNAL OF MOLECULAR BIOLOGY,436(22),16. |
| MLA | Wang, Wei-wei,et al."Structural Basis of Main Proteases of Coronavirus Bound to Bofutrelvir".JOURNAL OF MOLECULAR BIOLOGY 436.22(2024):16. |
入库方式： OAI收割
来源：上海药物研究所
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