65976-49-0Relevant academic research and scientific papers
Discovery, Optimization, and Target Identification of Novel Potent Broad-Spectrum Antiviral Inhibitors
Yang, Yiqing,Cao, Lin,Gao, Hongying,Wu, Yue,Wang, Yaxin,Fang, Fang,Lan, Tianlong,Lou, Zhiyong,Rao, Yu
, p. 4056 - 4073 (2019)
Viral infections are increasing and probably long-lasting global risks. In this study, a chemical library was exploited by phenotypic screening to discover new antiviral inhibitors. After optimizations from hit to lead, a novel potent small molecule (RYL-634) was identified, showing excellent broad-spectrum inhibition activity against various pathogenic viruses, including hepatitis C virus, dengue virus, Zika virus, chikungunya virus, enterovirus 71, human immunodeficiency virus, respiratory syncytial virus, and others. The mechanism of action and potential targets of RYL-634 were further explored by the combination of activity-based protein profiling and other techniques. Finally, human dihydroorotate dehydrogenase was validated as the major target of RYL-634. We did not observe any mutant resistance under our pressure selections with RYL-634, and it had a strong synergistic effect with some Food and Drug Administration-approved drugs. Hence, there is great potential for developing new broad-spectrum antivirals based on RYL-634.
