Viral proteases: Structure, mechanism and inhibition.

Viral proteases: Structure, mechanism and inhibition.
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DOI:
10.1016/bs.enz.2021.09.004
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发表时间:
2021
期刊:
The Enzymes
影响因子:
--
通讯作者:
Schiffer CA
Schiffer CA
中科院分区:
其他
文献类型:
--
作者:
Zephyr J;Kurt Yilmaz N;Schiffer CA

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病毒蛋白酶在结构、寡聚态、催化机制和底物特异性等方面具有多样性。本章重点介绍与人类健康相关的病毒的蛋白酶:人类免疫缺陷病毒1亚型(HIV-1)、丙型肝炎病毒(HCV)、人类t细胞白血病病毒1型(HTLV-1)、黄病毒、肠病毒和冠状病毒。HIV-1和HCV的蛋白酶已经成功地靶向治疗,目前临床上使用的是经fda批准的小摩尔药物。HTLV-1和其他病毒家族的蛋白酶在药物开发过程的不同阶段仍然是新兴的治疗靶点。本章概述了目前关于病毒蛋白酶结构、机制、底物识别和抑制的知识。特别关注的是了解不同底物识别和耐药性的分子基础的最新进展,这对于设计新型蛋白酶抑制剂作为抗病毒药物至关重要。
Viral proteases are diverse in structure, oligomeric state, catalytic mechanism, and substrate specificity. This chapter focuses on proteases from viruses that are relevant to human health: human immunodeficiency virus subtype 1 (HIV-1), hepatitis C (HCV), human T-cell leukemia virus type 1 (HTLV-1), flaviviruses, enteroviruses, and coronaviruses. The proteases of HIV-1 and HCV have been successfully targeted for therapeutics, with picomolar FDA-approved drugs currently used in the clinic. The proteases of HTLV-1 and the other virus families remain emerging therapeutic targets at different stages of the drug development process. This chapter provides an overview of the current knowledge on viral protease structure, mechanism, substrate recognition, and inhibition. Particular focus is placed on recent advances in understanding the molecular basis of diverse substrate recognition and resistance, which is essential toward designing novel protease inhibitors as antivirals.
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