Together with the existing knowledge on TDF pharmacokinetic/pharmacodynamics, our findings support that TDF, among tenofovir-based compounds, might maximize efficacy at safe clinical dosage especially when taken before or very close after exposure, because of their high cellular permeation, effective metabolite activation, and low-selective distribution at viral targeted tissues, laying out a plausible molecular interpretation of the apparent inconsistency of tenofovir-based compounds against SARS-CoV-2 [46].  Finally, our findings underscore the need for understanding the intracellular availability of the drugs in SARS-CoV2 targeted tissues to further evaluate remdesivir, TDF and other antivirals [12]