Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase

Steffen Jockusch; Chuanjuan Tao; Xiaoxu Li; Thomas K. Anderson; Minchen Chien; Shiv Kumar; James J. Russo; Robert Kirchdoerfer; Jingyue Ju

Tenofovir diphosphate (TFV-DP) and Emtricitabine triphosphate (Ec-TP) ( Fig. 1 c, g) are the active triphosphate forms of two viral reverse transcriptase inhibitors for HIV and hepatitis B virus (HBV). Gilead's TRUVADA and DESCOVY are two FDA-approved medications for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection. PrEP is a preventative method in which individuals who are HIV negative (but at high-risk of contracting the virus) take the combination drug daily to reduce the chance of becoming infected with HIV. [12] [13] [14] [15] Both TRUVADA and DESCOVY consist of the prodrugs, Emtricitabine (2',3'-dideoxy-5-fluoro-3'-thiacytidine, FTC) and either of two prodrug forms of Tenofovir (Tenofovir disoproxil fumarate (TDF) in TRUVADA and Tenofovir alafenamide (TAF) in DESCOVY). Overall, the combination drugs are well tolerated, with a small but significant reduction in the number of patients with side effects in the latter. 16 These drugs are often included in the cocktails for patients with HIV/AIDS. It is critical to ensure that those being administered these drugs for PrEP are HIV negative. Resistance mutations have been observed in a small percentage of individuals using FTC plus TDF. 17 It is therefore important to screen them for seroconversion and possible drug resistance.