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

  • J Med Chem. 2006 Aug 10;49(16):4971-80. doi: 10.1021/jm0603926.
Syaulan Yang  1 ,  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
Affiliations
  • 1. TaiGen Biotechnology Co., Taipei 114, Taiwan, ROC.
PMID: 16884309 DOI: 10.1021/jm0603926
Abstract

A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 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 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A) 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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