Coronavirus main proteinase (3CLpro) structure:: Basis for design of anti-SARS drugs
Coronavirus main proteinase (3CLpro) structure:: Basis for design of anti-SARS drugs
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DOI：
10.1126/science.1085658
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发表时间：
2003-06-13
期刊：
影响因子：
56.9
通讯作者：
Hilgenfeld, R
中科院分区：
文献类型：
--
作者：
Anand, K;Ziebuhr, J;Hilgenfeld, R
一种新型冠状病毒已被确定为严重急性呼吸综合征（SARS）的病原体。控制冠状病毒复制复合物活性的病毒主要蛋白酶（M-pro，也称为3CL（pro））是一种有吸引力的治疗靶点。我们确定了人冠状病毒（菌株229 E）M-pro和猪冠状病毒[传染性胃肠炎病毒（TGEV）] Mpro抑制剂复合物的晶体结构，并构建了SARS冠状病毒（SARS-CoV）M-pro的同源模型。这些结构揭示了底物结合位点的显著保守程度，这进一步得到了重组SARS-CoV M-pro介导的TGEV Mpro底物裂解的支持。分子模型表明，可用的鼻病毒3C（亲）抑制剂可以进行修改，使它们用于治疗SARS。
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.