Selected article for: "broad spectrum and late infection"

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_4
    Snippet: To identify potent and low-toxicity DHODH inhibitors (DHODHi), we previously conducted a hierarchal structure-based virtual screening (Fig. 1A) against ~280,000 compounds library towards the ubiquinone-binding site of DHODH 26 . We finally obtained two highly potent DHODHi S312 and S416 with IC50s of 29.2 nM and 7.5 nM through structural optimization 27, 28 , which are > 10-folds potent than the FDA approved DHODHi Teriflunomide (IC50 of 307.1 nM.....
    Document: To identify potent and low-toxicity DHODH inhibitors (DHODHi), we previously conducted a hierarchal structure-based virtual screening (Fig. 1A) against ~280,000 compounds library towards the ubiquinone-binding site of DHODH 26 . We finally obtained two highly potent DHODHi S312 and S416 with IC50s of 29.2 nM and 7.5 nM through structural optimization 27, 28 , which are > 10-folds potent than the FDA approved DHODHi Teriflunomide (IC50 of 307.1 nM). By using these two potent inhibitors, we could fully evaluate DHODH as a valuable host target both in infected cells and in vivo in infected animals. We identified that targeting DHODH offers broad-spectrum antiviral efficacies against various RNA viruses, including the DAA-resistant influenza virus and the newly emerged coronavirus SARS-CoV-2. Especially, our potent DHODHi can protect 100% mice from lethal influenza challenge, which is as good as the DAA drugs, and is even effective in the late phase of infection when DAA drug is no longer responding.

    Search related documents:
    Co phrase search for related documents