Selected article for: "complete culture medium and culture medium"
Author: Rui Xiong; Leike Zhang; Shiliang Li; Yuan Sun; Minyi Ding; Yong Wang; Yongliang Zhao; Yan Wu; Weijuan Shang; Xiaming Jiang; Jiwei Shan; Zihao Shen; Yi Tong; Liuxin Xu; Chen Yu; Yingle Liu; Gang Zou; Dimitri Lavillete; Zhenjiang Zhao; Rui Wang; Lili Zhu; Gengfu Xiao; Ke Lan; Honglin Li; Ke Xu
Title: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2
  • Document date: 2020_3_12
    • ID: hq5um68k_30
    Snippet: DHODH is a rate-limiting enzyme catalyzing the fourth step in pyrimidine de novo synthesis. It catalyzes the dehydrogenation of dihydroorotate (DHO) to orotic acid (ORO) to finally generate Uridine (U) and Cytosine (C) to supply nucleotide resources in a cell. Under normal conditions, nucleotides are supplied via both de novo biosynthesis and salvage pathways, the latter of which is a way of recycling pre-existing nucleotides from food or other n.....
    Document: DHODH is a rate-limiting enzyme catalyzing the fourth step in pyrimidine de novo synthesis. It catalyzes the dehydrogenation of dihydroorotate (DHO) to orotic acid (ORO) to finally generate Uridine (U) and Cytosine (C) to supply nucleotide resources in a cell. Under normal conditions, nucleotides are supplied via both de novo biosynthesis and salvage pathways, the latter of which is a way of recycling pre-existing nucleotides from food or other nutrition. However, in virus-infected cells, a large intracellular nucleotide pool is demanded by rapid viral replication. It is therefore reasonable that de novo nucleotides biosynthesis rather than salvage pathway is more critical for virus replication. Our data indeed show that virus replication is largely restricted when the DHODH gene was knocked off even with a complete culture medium. By contrast, cell growth was not affected by lacking DHODH at all, indicating that de novo nucleotides biosynthesis is not indispensable in normal cell growth without infection at least for days. More interestingly, we notice that compared with DNA viruses, RNA viruses need unique UMP but not TMP in their genomes. UMP is the . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . particular nucleoside produced by DHODH, which means RNA viruses might be more sensitive to DHODH activity. SARS-CoV-2, for instance, has around 32% of UMP in its genome explaining why DHODHi are effective and superior to SARS-CoV-2.

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