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Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro
[Image: see text] The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development o...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical Society
2023
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885526/ https://www.ncbi.nlm.nih.gov/pubmed/36844503 http://dx.doi.org/10.1021/acscentsci.2c01359 |
| _version_ | 1784879948008259584 |
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| author | Hou, Ningke Shuai, Lei Zhang, Lijing Xie, Xuping Tang, Kaiming Zhu, Yunkai Yu, Yin Zhang, Wenyi Tan, Qiaozhu Zhong, Gongxun Wen, Zhiyuan Wang, Chong He, Xijun Huo, Hong Gao, Haishan Xu, You Xue, Jing Peng, Chen Zou, Jing Schindewolf, Craig Menachery, Vineet Su, Wenji Yuan, Youlang Shen, Zuyuan Zhang, Rong Yuan, Shuofeng Yu, Hongtao Shi, Pei-Yong Bu, Zhigao Huang, Jing Hu, Qi |
| author_facet | Hou, Ningke Shuai, Lei Zhang, Lijing Xie, Xuping Tang, Kaiming Zhu, Yunkai Yu, Yin Zhang, Wenyi Tan, Qiaozhu Zhong, Gongxun Wen, Zhiyuan Wang, Chong He, Xijun Huo, Hong Gao, Haishan Xu, You Xue, Jing Peng, Chen Zou, Jing Schindewolf, Craig Menachery, Vineet Su, Wenji Yuan, Youlang Shen, Zuyuan Zhang, Rong Yuan, Shuofeng Yu, Hongtao Shi, Pei-Yong Bu, Zhigao Huang, Jing Hu, Qi |
| author_sort | Hou, Ningke |
| collection | PubMed |
| description | [Image: see text] The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC(50) values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. |
| format | Online Article Text |
| id | pubmed-9885526 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | American Chemical Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-98855262023-01-30 Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro Hou, Ningke Shuai, Lei Zhang, Lijing Xie, Xuping Tang, Kaiming Zhu, Yunkai Yu, Yin Zhang, Wenyi Tan, Qiaozhu Zhong, Gongxun Wen, Zhiyuan Wang, Chong He, Xijun Huo, Hong Gao, Haishan Xu, You Xue, Jing Peng, Chen Zou, Jing Schindewolf, Craig Menachery, Vineet Su, Wenji Yuan, Youlang Shen, Zuyuan Zhang, Rong Yuan, Shuofeng Yu, Hongtao Shi, Pei-Yong Bu, Zhigao Huang, Jing Hu, Qi ACS Cent Sci [Image: see text] The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC(50) values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. American Chemical Society 2023-01-25 /pmc/articles/PMC9885526/ /pubmed/36844503 http://dx.doi.org/10.1021/acscentsci.2c01359 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
| spellingShingle | Hou, Ningke Shuai, Lei Zhang, Lijing Xie, Xuping Tang, Kaiming Zhu, Yunkai Yu, Yin Zhang, Wenyi Tan, Qiaozhu Zhong, Gongxun Wen, Zhiyuan Wang, Chong He, Xijun Huo, Hong Gao, Haishan Xu, You Xue, Jing Peng, Chen Zou, Jing Schindewolf, Craig Menachery, Vineet Su, Wenji Yuan, Youlang Shen, Zuyuan Zhang, Rong Yuan, Shuofeng Yu, Hongtao Shi, Pei-Yong Bu, Zhigao Huang, Jing Hu, Qi Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro |
| title | Development of
Highly Potent Noncovalent Inhibitors
of SARS-CoV-2 3CLpro |
| title_full | Development of
Highly Potent Noncovalent Inhibitors
of SARS-CoV-2 3CLpro |
| title_fullStr | Development of
Highly Potent Noncovalent Inhibitors
of SARS-CoV-2 3CLpro |
| title_full_unstemmed | Development of
Highly Potent Noncovalent Inhibitors
of SARS-CoV-2 3CLpro |
| title_short | Development of
Highly Potent Noncovalent Inhibitors
of SARS-CoV-2 3CLpro |
| title_sort | development of
highly potent noncovalent inhibitors
of sars-cov-2 3clpro |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885526/ https://www.ncbi.nlm.nih.gov/pubmed/36844503 http://dx.doi.org/10.1021/acscentsci.2c01359 |
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