Cell-Dependent Activation of ProTide Prodrugs and Its Implications in Antiviral Studies

The ProTide prodrug design is a powerful tool to improve cell permeability and enhance the intracellular activation of nucleotide antiviral analogues. Previous in vitro studies showed that prodrugs varied different lines. In present study, we investigated profiles two tenofovir alafenamide (TAF) sofosbuvir (SOF) five lines commonly used research, namely, Vero E6, Huh-7, Calu-3, A549, Caco-2. We found TAF SOF were activated cell-dependent manner with E6 being least efficient Huh-7 most line for activating prodrugs. also demonstrated was at significantly higher rate than SOF. further analyzed protein expressions enzymes carboxylesterase 1, cathepsin A, histidine triad nucleotide-binding relevant drug transporters P-glycoprotein organic anion-transporting polypeptides 1B1 1B3 using proteomics data extracted from literature proteome database. results revealed significant differences expression patterns among lines, which might partially contribute observed These findings highlight variability abundance between emphasize importance selecting appropriate assessing efficacy nucleoside/nucleotide