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ShanghaiTech University Knowledge Management System
| Discovery of Novel Nonpeptidic and Noncovalent Small Molecule 3CLpro Inhibitors as anti-SARS-CoV-2 Drug Candidate | |
| 2024-07-29 | |
| 发表期刊 | JOURNAL OF MEDICINAL CHEMISTRY (IF:6.8[JCR-2023],7.1[5-Year]) |
| ISSN | 0022-2623 |
| EISSN | 1520-4804 |
| 卷号 | 67期号:15 |
| 发表状态 | 已发表 |
| DOI | 10.1021/acs.jmedchem.4c00739 |
| 摘要 | SARS-CoV-2 has still been threatening global public health with its emerging variants. Our previous work reported lead compound JZD-07 that displayed good 3CL(pro) inhibitory activity. Here, an in-depth structural optimization for JZD-07 was launched to obtain more desirable drug candidates for the therapy of SARS-CoV-2 infection, in which 54 novel derivatives were designed and synthesized by a structure-based drug design strategy. Among them, 24 compounds show significantly enhanced 3CL(pro) inhibitory potencies with IC50 values less than 100 nM, and 11 compounds dose-dependently inhibit the replication of the SARS-CoV-2 delta variant. In particular, compound 49 has the most desirable antiviral activity with EC50 of 0.272 +/- 0.013 mu M against the delta variant, which was more than 20 times stronger than JZD-07. Oral administration of 49 could significantly reduce the lung viral copies of mice, exhibiting a more favorable therapeutic potential. Overall, this investigation presents a promising drug candidate for further development to treat SARS-CoV-2 infection. |
| URL | 查看原文 |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助项目 | National Natural Science Foundation of China[ |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Medicinal |
| WOS记录号 | WOS:001280437200001 |
| 出版者 | AMER CHEMICAL SOC |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/408306 |
| 专题 | 物质科学与技术学院 生命科学与技术学院 生命科学与技术学院_博士生 物质科学与技术学院_博士生 |
| 共同第一作者 | Feng, Bo; Chen, Lu; Nie, Tianqing |
| 通讯作者 | Zang, Yi; Su, Haixia; Zhang, Leike; Li, Jia; Zhou, Yu |
| 作者单位 | 1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Lingang Lab, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China 6.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.China Three Gorges Univ, Coll Biol & Pharmaceut Sci, Yichang 443002, Hubei, Peoples R China 9.Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, Ctr Biosafety Megasci, Wuhan 430071, Peoples R China 10.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 11.Henan Univ, Pharmaceut Coll, Kaifeng 475004, Peoples R China 12.Hubei Jiangxia Lab, Wuhan 430200, Peoples R China 13.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China |
| 第一作者单位 | 生命科学与技术学院 |
| 通讯作者单位 | 生命科学与技术学院 |
| 第一作者的第一单位 | 生命科学与技术学院 |
| 推荐引用方式 GB/T 7714 | Jiang, Zhidong,Feng, Bo,Chen, Lu,et al. Discovery of Novel Nonpeptidic and Noncovalent Small Molecule 3CLpro Inhibitors as anti-SARS-CoV-2 Drug Candidate[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024,67(15). |
| APA | Jiang, Zhidong.,Feng, Bo.,Chen, Lu.,Nie, Tianqing.,Chen, Shizhao.,...&Zhou, Yu.(2024).Discovery of Novel Nonpeptidic and Noncovalent Small Molecule 3CLpro Inhibitors as anti-SARS-CoV-2 Drug Candidate.JOURNAL OF MEDICINAL CHEMISTRY,67(15). |
| MLA | Jiang, Zhidong,et al."Discovery of Novel Nonpeptidic and Noncovalent Small Molecule 3CLpro Inhibitors as anti-SARS-CoV-2 Drug Candidate".JOURNAL OF MEDICINAL CHEMISTRY 67.15(2024). |
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