Coronavirus main proteinase (3CLpro) structure:: Basis for design of anti-SARS drugs

被引：1376

作者：

Anand, K

Ziebuhr, J

Wadhwani, P

Mesters, JR

Hilgenfeld, R

机构：

[1] Univ Lubeck, Inst Biochem, D-23538 Lubeck, Germany

[2] Inst Mol Biotechnol, D-07745 Jena, Germany

[3] Univ Wurzburg, Inst Virol & Immunol, D-97078 Wurzburg, Germany

[4] Univ Jena, Inst Mol Biol, D-07745 Jena, Germany

来源：

SCIENCE | 2003年 / 300卷 / 5626期

关键词：

D O I：

10.1126/science.1085658

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (M-pro, also called 3CL(pro)), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) M-pro and for an inhibitor complex of porcine coronavirus [ transmissible gastroenteritis virus ( TGEV)] Mpro, and we constructed a homology model for SARS coronavirus (SARS-CoV) M-pro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV M-pro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3C(pro) inhibitors may be modified to make them useful for treating SARS.

引用

页码：1763 / 1767

页数：5

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