二氢乳清酸脱氢酶抑制剂抗病毒机制的研究进展  

Research Progress on Antiviral Mechanisms of Dihydroorotate Dehydrogenase Inhibitors

作　　者：任小利 刘小勇 陈惺 戴妍 杨兵 陈静霞 王文斌 REN Xiaoli;LIU Xiaoyong;CHEN Xing;DAI Yan;YANG Bing;CHEN Jingxia;WANG Wenbing(School of Environment and Quality Inspection,Chongqing Industry Vocational College,Chongqing 401228,China;Research Institute of Surgery,Third Military Medical University,Chongqing 400042,China)

机构地区：[1]重庆化工职业学院环境与质量检测学院,重庆401228 [2]陆军军医大学野战外科研究所,重庆400042

出　　处：《病毒学报》2023年第3期829-838,共10页Chinese Journal of Virology

基　　金：重庆市教育委员会科学技术研究项目(项目号:KJQN202204506,KJQN202004503),题目:抗自身免疫性疾病药物—人二氢乳清酸脱氢酶抑制剂的优化;抗SARS-CoV-2药物h DHODH抑制剂的筛选。

摘　　要：各种病毒的持续暴发提示我们必须准备好广谱抗病毒药物。病毒复制必须通过宿主细胞提供原料,因此靶向宿主抗病毒(Host-targeting antiviral, HTA)药物具有广谱性、前瞻性和低耐药性,其前景广阔。研究发现,宿主二氢乳清酸脱氢酶(Dihydroorotate dehydrogenase, DHODH)是许多急性感染性病毒复制所必需的普遍宿主因子之一。DHODH是一种限速酶,催化嘧啶从头合成途径的第四步反应。因此,它也被开发为许多依赖细胞嘧啶资源疾病的治疗靶点,如自身免疫性疾病、病毒或细菌感染。值得注意的是,DHODH抑制剂(Dihydroorotate dehydrogenase inhibitor, DHODHi)对新型冠状病毒(Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)也有抑制作用。本文综述了DHODHi抗病毒的原理和抗病毒机制,期待能为DHODHi的开发提供帮助,早日研发出更多广谱抗病毒新药。Continuous outbreak of various virus diseases suggests that broad-spectrum antiviral drugs are highly required.Viral replication rely on raw materials is provided by host cells,so host targeting antiviral(HTA)drugs are broad spectrum,prospective and low drug resistance,with broad prospects.It has been found that the host dihydroorotate dehydrogenase(DHODH)is one of the universal host factors necessary for the replication of many acute infectious viruses.DHODH is a rate limiting enzyme that catalyzes the fourth step of de novo synthesis of pyrimidine.Therefore,it has also been developed as a therapeutic target for many diseases that depend on cytosine resources,such as autoimmune diseases,viral or bacterial infections.It is worth noting that DHODH inhibitor(DHODHi)also has inhibitory effect on Severe acute respiratory syndrome coronavirus 2(SARS CoV-2).This article summarizes the anti-virus principle and anti-viral mechanisms of DHODHi,aiming to provide help for the development of DHODHi and more broad-spectrum anti-virus drugs.

关 键 词：DHODH抑制剂(DHODHi) 新型冠状病毒(SARS-CoV-2) 广谱抗病毒药 靶向宿主因子抗病毒(HTA) 嘧啶合成 

分 类 号：R963[医药卫生—微生物与生化药学] R373.9[医药卫生—药理学]