JOURNAL ARTICLE

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
Journal of Medicinal Chemistry 2006 August 10, 49 (16): 4971-80
16884309
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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
16884309
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"