In particular, tenofovir disoproxil (Viread; 2001) is an adenine-based acyclic nucleotide analog (Figure S1) that, following activation, acts as a competitive inhibitor of reverse transcriptase, and subsequently, it leads to DNA chain elongation termination. Activation of the drug starts with the hydrolysis of the external esters followed by spontaneous release of carbon dioxide and formaldehyde to form the corresponding tenofovir, a nucleoside monophosphate, which subsequently undergoes two phosphorylation steps to form tenofovir diphosphate, the active drug (Figure S1) [64]. It was first approved in 2001 by the U.S. FDA and is prescribed for the oral treatment of HIV-1 and chronic HBV infections [65]. It is also available in many other combinations with emtricitabine, lamivudine (Cimduo; 2018), doravirine and lamivudine (Delstrigo; 2018), and efavirenz and lamivudine (Symfi; 2018). The efficacy of emtricitabine and tenofovir disoproxil 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 (NCT04334928). The two drugs have been reported by a recent computational work as potential inhibitors of RdRp of SARS-CoV-2 [55,66], yet this potential is to be experimentally confirmed.