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. Peters^*

Andrew H.J. Wang, Ming Chu Hsu

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

145 Scopus citations

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 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.

Original language	English
Pages (from-to)	4971-4980
Number of pages	10
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	16
DOIs	https://doi.org/10.1021/jm0603926
State	Published - 10 08 2006
Externally published	Yes

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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

@article{254a990ab90748b68410607590fd901f,

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

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\}",

year = "2006",

month = aug,

day = "10",

doi = "10.1021/jm0603926",

language = "英语",

volume = "49",

pages = "4971--4980",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "16",

}

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, vol. 49, no. 16, pp. 4971-4980. https://doi.org/10.1021/jm0603926

TY - JOUR

T1 - Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor

AU - Yang, Syaulan

AU - Chen, Shu Jen

AU - Hsu, Min Feng

AU - Wu, Jen Dar

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

Y1 - 2006/8/10

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/33746886624

U2 - 10.1021/jm0603926

DO - 10.1021/jm0603926

M3 - 文章

C2 - 16884309

AN - SCOPUS:33746886624

SN - 0022-2623

VL - 49

SP - 4971

EP - 4980

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 16

ER -

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

Abstract

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