State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
State Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Viruses. 2022 Apr 28;14(5):928. doi: 10.3390/v14050928.
New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.
新策略迫切需要迅速开发广谱抗病毒疗法，以应对新兴和重现的病毒。靶向宿主的抗病毒药物（HTAs）是最有前途的方法之一，具有广谱、前瞻性的功能和低耐药性。我们和其他人最近发现，宿主二氢乳清酸脱氢酶（DHODH）是许多急性感染病毒复制所必需的通用宿主因子之一。DHODH 是催化嘧啶合成第四步的限速酶。因此，它也被开发为依赖于细胞嘧啶资源的许多疾病的治疗靶点，如癌症、自身免疫性疾病、病毒或细菌感染。重要的是，DHODH 抑制剂（DHODHi）成功用于治疗严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染，进一步支持了其应用前景。本综述重点介绍了 HTAs 的优势和具有临床应用的 DHODHi 的抗病毒作用。DHODHi 通过抑制病毒复制、刺激 ISGs 表达和抑制细胞因子风暴来发挥多种功能，使其成为对抗病毒感染的有效策略。
