Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy.
Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy.
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DOI：
10.1016/s0065-7743(06)41011-3
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发表时间：
2007-02-01
影响因子：
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通讯作者：
Mesecar, Andrew D.
中科院分区：
文献类型：
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作者：
Ghosh, Arun K.;Xi, Kai;Johnson, Michael E.;Baker, Susan C.;Mesecar, Andrew D.
冠状病毒复制酶多蛋白的蛋白水解性处理对于正在进行的病毒核糖核酸(RNA)合成是必不可少的。因此，严重急性呼吸综合征(SARS)冠状病毒(SARS-CoV)蛋白水解酶是开发抗病毒药物以降低病毒复制和致病性的有吸引力的靶点。冠状病毒3C型蛋白水解酶(3CLpro)的结构和活性已被阐明，并提出了设计3CLpro的抑制剂作为治疗药物。本章讨论了SARS-CoV 3CLPro抑制剂，包括共价抑制剂、非共价抑制剂和筛选出的抑制剂。SARS冠状病毒类木瓜蛋白酶(PLPro)被认为是3CLPro药物设计的同样可行的靶标，因为两者都是病毒复制所必需的。然而，由于缺乏结构性信息，PLPro很可能没有受到追捧。已鉴定出几个化合物具有抑制SARS-CoV的活性。然而，关于它们的作用机制或相应的目标的信息尚不清楚。甘草酸苷在Vero细胞中对SARS冠状病毒复制有抑制作用，其EC50=300 mg/L。一些甘草酸衍生物在体外具有抑制SARS冠状病毒复制的作用，其EC50值在5~50μM之间。
Proteolytic processing of the coronavirus replicase polyproteins is essential for ongoing viral ribonucleic acid (RNA) synthesis. Therefore, the severe acute respiratory syndrome (SARS)-coronaviruses (SARS-CoV) proteases are attractive targets for the development of antiviral drugs to reduce viral replication and pathogenicity. The structure and activity of the coronavirus 3C-like protease (3CLpro) has already been elucidated, and the design of inhibitors to 3CLpro as therapeutics has been proposed. The chapter discusses SARS-CoV 3CLpro inhibitors that include covalent inhibitors, noncovalent inhibitors, and inhibitors from screening. SARS-CoV papain-like protease (PLpro) is considered an equally viable target to 3CLpro for drug design because both are essential for viral replication. However, PLpro has likely not been pursued because of the paucity of structural information. Several compounds have been identified that have shown inhibitory activity against SARS-CoV. However, no information regarding their mechanism of action or the corresponding target is known. Glycyrrhizin showed inhibitory activity for SARS-CoV replication with EC50 = 300 mg/L after virus absorption in Vero cells. Some glycyrrhizin acid derivatives were found to inhibit SARS-CoV replication in vitro with EC50 values ranging from 5 to 50 μM. Unfortunately, these compounds show high cytotoxity.