3C和3CL蛋白酶及广谱抑制剂的研究进展  

Broad spectrum inhibitors of 3C and 3CL proteases:research advances

作　　者：张启燕 张文会[1,2] 肖军海[2] 李松[1,2] 

机构地区：[1]沈阳药科大学制药工程学院,沈阳110016 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《国际药学研究杂志》2016年第3期425-430,共6页Journal of International Pharmaceutical Research

摘　　要：小RNA病毒和冠状病毒属于单正链RNA病毒,其家族中的病原体易导致手足口病、心肌炎、普通感冒以及严重的呼吸道和肠道疾病。3C和3CL蛋白酶都属于半胱氨酸蛋白酶,底物结合位点高度保守且具有相似的催化机制,是催化单正链RNA病毒前体蛋白裂解的关键蛋白酶,对病毒的复制有重要作用。人体中没有与其相似的蛋白酶,是目前广谱抗单正链RNA病毒研究的重要靶点。利用3C和3CL蛋白酶结构的相同点,成功发现了具有广谱作用的蛋白酶抑制剂。本文简要概述3C和3CL蛋白酶的结构、功能和广谱抑制剂的研究进展,并简要阐释抑制剂的作用机制,对该类酶的广谱抑制剂研究和相关病毒的治疗具有指导意义。Picornaviruses（PV）and coronaviruses（CoV） are positive-stranded RNA viruses. Pathogens in the family can cause hand,foot and mouth disease,myocarditis, common cold ,severe respiratory and intestinal diseases. 3C and 3CL proteases, belonging to cysteine proteases,are required to process polyproteins into mature proteins for viral replication,which plays an impor？tant role in viral replication because substrate binding sites are highly conservative and have similar catalytic mechanism. 3C and 3CL proteases are different from protease in the human body ,which represents a promising anti-viral drug target. Using 3C and 3CL pro？teinase structural similarities,broad spectrum protease inhibitors have been found successfully. This review describes recent develop？ments of broad spectrum protease inhibitors targeting on 3C and 3CL proteases,and briefly illustrates the mechanism of the inhibitors, which may benefit to the development of virus therapy.

关 键 词：RNA病毒 3C蛋白酶 3CL蛋白酶 广谱抑制剂 

分 类 号：R978.7[医药卫生—药品]