FIG 4.
Correlation between CatA-mediated hydrolysis and antiretroviral activity of phosphonoamidate prodrugs of TFV. TAF and a panel of 48 different phosphonoamidate prodrugs of TFV were incubated with CatA to determine the rate of hydrolysis of the prodrugs. The corresponding antiviral activity for each compound was determined from quadruplicate measurements using a 5-day cytopathic assay in HIV-1-infected MT-4 cells. EC50s, determined from at least two independent experiments, represent the mean drug concentration providing 50% protection against the cytopathic effects associated with HIV-1 (IIIb) replication.