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Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease
SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (M(pro)) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting M(pro). Both e...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Association for the Advancement of Science
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179937/ https://www.ncbi.nlm.nih.gov/pubmed/32321856 http://dx.doi.org/10.1126/science.abb4489 |
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| author | Dai, Wenhao Zhang, Bing Su, Haixia Li, Jian Zhao, Yao Xie, Xiong Jin, Zhenming Liu, Fengjiang Li, Chunpu Li, You Bai, Fang Wang, Haofeng Cheng, Xi Cen, Xiaobo Hu, Shulei Yang, Xiuna Wang, Jiang Liu, Xiang Xiao, Gengfu Jiang, Hualiang Rao, Zihe Zhang, Lei-Ke Xu, Yechun Yang, Haitao Liu, Hong |
| author_facet | Dai, Wenhao Zhang, Bing Su, Haixia Li, Jian Zhao, Yao Xie, Xiong Jin, Zhenming Liu, Fengjiang Li, Chunpu Li, You Bai, Fang Wang, Haofeng Cheng, Xi Cen, Xiaobo Hu, Shulei Yang, Xiuna Wang, Jiang Liu, Xiang Xiao, Gengfu Jiang, Hualiang Rao, Zihe Zhang, Lei-Ke Xu, Yechun Yang, Haitao Liu, Hong |
| author_sort | Dai, Wenhao |
| collection | PubMed |
| description | SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (M(pro)) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting M(pro). Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The X-ray crystal structures of SARS-CoV-2 M(pro) in complex with 11a or 11b, both determined at 1.5 Å resolution, showed that the aldehyde groups of 11a and 11b are covalently bound to Cys145 of M(pro). Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity, suggesting that these compounds are promising drug candidates. |
| format | Online Article Text |
| id | pubmed-7179937 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-71799372020-04-23 Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease Dai, Wenhao Zhang, Bing Su, Haixia Li, Jian Zhao, Yao Xie, Xiong Jin, Zhenming Liu, Fengjiang Li, Chunpu Li, You Bai, Fang Wang, Haofeng Cheng, Xi Cen, Xiaobo Hu, Shulei Yang, Xiuna Wang, Jiang Liu, Xiang Xiao, Gengfu Jiang, Hualiang Rao, Zihe Zhang, Lei-Ke Xu, Yechun Yang, Haitao Liu, Hong Science Research Articles SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (M(pro)) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting M(pro). Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The X-ray crystal structures of SARS-CoV-2 M(pro) in complex with 11a or 11b, both determined at 1.5 Å resolution, showed that the aldehyde groups of 11a and 11b are covalently bound to Cys145 of M(pro). Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity, suggesting that these compounds are promising drug candidates. American Association for the Advancement of Science 2020-04-22 /pmc/articles/PMC7179937/ /pubmed/32321856 http://dx.doi.org/10.1126/science.abb4489 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
| spellingShingle | Research Articles Dai, Wenhao Zhang, Bing Su, Haixia Li, Jian Zhao, Yao Xie, Xiong Jin, Zhenming Liu, Fengjiang Li, Chunpu Li, You Bai, Fang Wang, Haofeng Cheng, Xi Cen, Xiaobo Hu, Shulei Yang, Xiuna Wang, Jiang Liu, Xiang Xiao, Gengfu Jiang, Hualiang Rao, Zihe Zhang, Lei-Ke Xu, Yechun Yang, Haitao Liu, Hong Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease |
| title | Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease |
| title_full | Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease |
| title_fullStr | Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease |
| title_full_unstemmed | Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease |
| title_short | Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease |
| title_sort | structure-based design of antiviral drug candidates targeting the sars-cov-2 main protease |
| topic | Research Articles |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179937/ https://www.ncbi.nlm.nih.gov/pubmed/32321856 http://dx.doi.org/10.1126/science.abb4489 |
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