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

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

Surface plasmon resonance experiments were performed with a BIAcore T200 (GE Healthcare) according to our previous work 53 . The running buffer contained 1.05×PBS, 0.005% (vol/vol) surfactant P20, pH 7.4, and 1% DMSO. The purified DHODH, which was diluted in sodium acetate solution (pH 5.5) with a final concentration of 30 μg/mL, was immobilized on a CM5 sensor chip by amine coupling. All analyte measurements were performed at a flow rate of 30 μL/min. The analyte was diluted in the running buffer from the top concentration. Data processing and analysis were performed using BIAevaluation 1.1 software. Data were processed with Graphpad prism software to calculate EC50 and CC50 values of the compounds.