Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor
Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor
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DOI：
10.1021/jm0603926
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发表时间：
2006-08-10
影响因子：
7.3
通讯作者：
Hsu, Ming-Chu
中科院分区：
文献类型：
--
作者：
Yang, Syaulan;Chen, Shu-Jen;Hsu, Ming-Chu
研制出一种有效的SARS冠状病毒3CL蛋白酶抑制剂（TG- 0205221, K-i = 53 nM）。TG- 0205221对SARS CoV和人类冠状病毒（HCoV） 229E复制具有显著的抑制活性，对SARS CoV和HCoV 229E复制的病毒滴度分别降低4.7 log （5 μ M）和5.2 log （1.25 μ M）。TG- 0205221的晶体结构（分辨率为1.93埃）揭示了一种独特的结合模式，包括共价键、氢键和许多疏水相互作用。还讨论了TG- 0205221与天然肽底物的结构比较。这一信息可用于其它3CL蛋白酶抑制剂的设计。
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 mu M) for SARS CoV and 5.2 log (at 1.25 mu M) for HCoV 229E. The crystal structure of TG- 0205221 (resolution = 1.93 angstrom) 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.