Likewise, tenofovir alafenamide (Vemlidy; 2016) is an adenine-based acyclic nucleotide analog that, following activation, acts as a competitive inhibitor of reverse transcriptase and DNA chain elongation termination. The activation of the drug is, however, different and it usually takes place in infected cells by a series of bio-transformations similar to those of remdesivir (Figure S2) [67]. The main advantage of the prodrug, relative to the former prodrug, is that it increases the drug’s oral bioavailability, intestinal diffusion, selectivity of targeting the infected cells, and intracellular half-life. It also decreases the potential renal toxicity of the monophosphate intermediate. Tenofovir alafenamide was first approved in 2016 by the U.S. FDA and is prescribed for the oral treatment of HBV infection [68]. It is also available in many other combinations with emtricitabine (Descovy; 2016), bictegravir and emtricitabine (Biktarvy; 2018), emtricitabine and rilpivirine (Odefsey; 2016), and darunavir/cobicistat and emtricitabine (Symtuza; 2018). The efficacy of emtricitabine and tenofovir alafenamide as a prophylactic combination against SARS-CoV-2 infection is being evaluated in a large randomized, double-blind, controlled with placebo clinical trial for health care providers exposed to COVID-19 patients (NCT04405271; n = 1378).