Biochemical Effect of Resistance Mutations against Synergistic Inhibitors of RSV RNA Polymerase

@inproceedings{Deval2016BiochemicalEO,
  title={Biochemical Effect of Resistance Mutations against Synergistic Inhibitors of RSV RNA Polymerase},
  author={Jerome Deval and Amy Fung and Sarah K. Stevens and Paul C Jordan and Tatiana Gromova and Joshua S Taylor and Jin Hong and J. R. Meng and Guangyi Wang and Natalia Dyatkina and Marija Prhavc and Julian A. Symons and Leo Beigelman},
  booktitle={PloS one},
  year={2016}
}
ALS-8112 is the parent molecule of ALS-8176, a first-in-class nucleoside analog prodrug effective in the clinic against respiratory syncytial virus (RSV) infection. The antiviral activity of ALS-8112 is mediated by its 5'-triphosphate metabolite (ALS-8112-TP, or 2'F-4'ClCH2-cytidine triphosphate) inhibiting the RNA polymerase activity of the RSV L-P protein complex through RNA chain termination. Four amino acid mutations in the RNA-dependent RNA polymerase (RdRp) domain of L (QUAD: M628L, A789V… CONTINUE READING