Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor

Syaulan Yang; Shu Jen Chen; Min Feng Hsu; Jen Dar Wu; Chien Te K. Tseng; Yu Fan Liu; Hua Chien Chen; Chun Wei Kuo; Chi Shen Wu; Li Wen Chang; Wen Chang Chen; Shao Ying Liao; Teng Yuan Chang; Hsin Hui Hung; Hui Lin Shr; Cheng Yuan Liu; Yu An Huang; Ling Yin Chang; Jen Chi Hsu; Clarence J. Peters; Andrew H.J. Wang; Ming Chu Hsu

doi:10.1021/jm0603926

Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor

Syaulan Yang, Shu Jen Chen, Min Feng Hsu, Jen Dar Wu, Chien Te K. Tseng, Yu Fan Liu, Hua Chien Chen, Chun Wei Kuo, Chi Shen Wu, Li Wen Chang, Wen Chang Chen, Shao Ying Liao, Teng Yuan Chang, Hsin Hui Hung, Hui Lin Shr, Cheng Yuan Liu, Yu An Huang, Ling Yin Chang, Jen Chi Hsu, Clarence J. PetersAndrew H.J. Wang, Ming Chu Hsu

研究成果: 雜誌貢獻 › 文章 › 同行評審

130 引文斯高帕斯（Scopus）

摘要

A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, K _i = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 μM) for SARS CoV and 5.2 log (at 1.25 μM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 Å) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.

原文	英語
頁（從 - 到）	4971-4980
頁數	10
期刊	Journal of Medicinal Chemistry
卷	49
發行號	16
DOIs	https://doi.org/10.1021/jm0603926
出版狀態	已發佈 - 8月 10 2006
對外發佈	是

ASJC Scopus subject areas

分子醫學
藥物發現

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10.1021/jm0603926

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Yang, S., Chen, S. J., Hsu, M. F., Wu, J. D., Tseng, C. T. K., Liu, Y. F., Chen, H. C., Kuo, C. W., Wu, C. S., Chang, L. W., Chen, W. C., Liao, S. Y., Chang, T. Y., Hung, H. H., Shr, H. L., Liu, C. Y., Huang, Y. A., Chang, L. Y., Hsu, J. C., ... Hsu, M. C. (2006). Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor. Journal of Medicinal Chemistry, 49(16), 4971-4980. https://doi.org/10.1021/jm0603926

Yang, S, Chen, SJ, Hsu, MF, Wu, JD, Tseng, CTK, Liu, YF, Chen, HC, Kuo, CW, Wu, CS, Chang, LW, Chen, WC, Liao, SY, Chang, TY, Hung, HH, Shr, HL, Liu, CY, Huang, YA, Chang, LY, Hsu, JC, Peters, CJ, Wang, AHJ & Hsu, MC 2006, 'Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor', Journal of Medicinal Chemistry, 卷 49, 編號 16, 頁 4971-4980. https://doi.org/10.1021/jm0603926

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abstract = "A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, K i = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 μM) for SARS CoV and 5.2 log (at 1.25 μM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 {\AA}) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.",

author = "Syaulan Yang and Chen, {Shu Jen} and Hsu, {Min Feng} and Wu, {Jen Dar} and Tseng, {Chien Te K.} and Liu, {Yu Fan} and Chen, {Hua Chien} and Kuo, {Chun Wei} and Wu, {Chi Shen} and Chang, {Li Wen} and Chen, {Wen Chang} and Liao, {Shao Ying} and Chang, {Teng Yuan} and Hung, {Hsin Hui} and Shr, {Hui Lin} and Liu, {Cheng Yuan} and Huang, {Yu An} and Chang, {Ling Yin} and Hsu, {Jen Chi} and Peters, {Clarence J.} and Wang, {Andrew H.J.} and Hsu, {Ming Chu}",

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AU - Yang, Syaulan

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AU - Tseng, Chien Te K.

AU - Liu, Yu Fan

AU - Chen, Hua Chien

AU - Kuo, Chun Wei

AU - Wu, Chi Shen

AU - Chang, Li Wen

AU - Chen, Wen Chang

AU - Liao, Shao Ying

AU - Chang, Teng Yuan

AU - Hung, Hsin Hui

AU - Shr, Hui Lin

AU - Liu, Cheng Yuan

AU - Huang, Yu An

AU - Chang, Ling Yin

AU - Hsu, Jen Chi

AU - Peters, Clarence J.

AU - Wang, Andrew H.J.

AU - Hsu, Ming Chu

PY - 2006/8/10

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AB - A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, K i = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 μM) for SARS CoV and 5.2 log (at 1.25 μM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 Å) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.

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Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor

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