Potential treatment of COVID-19 by inhibitors of human dihydroorotate\xa0dehydrogenase

Yechun Xu,Hualiang Jiang

doi:10.1007/s13238-020-00769-9

Abstract

Potential treatment of COVID-19 by inhibitors of human dihydroorotate\xa0dehydrogenase

Highlights

Pyrimidines serve as crucial building blocks for the biosynthesis of DNA, RNA, phospholipids, and glycoproteins, which is essential for the cell survival as well as proliferation (Loffler et al, 2005)
In a remarkable study published in this journal, Xiong et al reported novel and potent inhibitors of human dihydroorotate dehydrogenase (DHODH) as broad-spectrum antiviral agents against RNA viruses including SARS-CoV-2 (Xiong et al, 2020)
Human DHODH belongs to the class 2 DHODH family and is a flavin-dependent mitochondrial enzyme catalyzing the oxidation of dihydroorotate to orotate, the fourth step a rate limiting step in the de novo biosynthesis of pyrimidine-based nucleotides (Reis et al, 2017) (Fig. 1A)

Summary

Introduction

Pyrimidines serve as crucial building blocks for the biosynthesis of DNA, RNA, phospholipids, and glycoproteins, which is essential for the cell survival as well as proliferation (Loffler et al, 2005). In addition to DAA drugs, host-targeting antiviral (HTA) agents, targeting host proteins required for the viral infection and replication, have advantages in overcoming drug resistance and combating a broad spectrum of viruses including the newly emerging virus (Ji and Li, 2020). In a remarkable study published in this journal, Xiong et al reported novel and potent inhibitors of human dihydroorotate dehydrogenase (DHODH) as broad-spectrum antiviral agents against RNA viruses including SARS-CoV-2 (Xiong et al, 2020).

Results

Conclusion