SAR evolution towards potent C-terminal carboxamide peptide inhibitors of Zika virus NS2B-NS3 protease
Zika virus (ZIKV) is a member of the Flaviviridae family that can cause neurological disorders and congenital malformations.
Our recent study published in the Journal of Pharmaceutical and Biomedical Analysis details a novel protocol using NMR for plasma protein binding (PPB) assessment in drug discovery research. PPB is the degree to which therapeutics attach to proteins in the blood plasma. The less a drug binds to protein in plasma, the stronger the therapeutic effect, and the faster its metabolism. If accurate, PPB assessment can facilitate the prediction of drug efficacy or toxicity – demonstrating the importance of PPB measurements in the drug discovery and development pipeline.
Current methods have significant drawbacks, such as long experiment duration and the use of purified proteins. As PPB calculations are typically undertaken in the earlier stages of the pipeline, it is critical to ensure that calculations are rapid, cost-effective and accurate. Our new method achieves all of these goals by using NMR to measure PBB in blood plasma, a physiologically relevant setting.