Amprenavir

In chronically infected monocyte‑derived macrophages, clinically relevant concentrations of amprenavir (4 and 20 µM) drastically reduced p24 production from day 2 to day 12 after administration. After drug removal, p24 levels increased but never reached those of untreated macrophages, indicating persistent intracellular activity. Moreover, HIV‑1 infectivity and the p24/p55 ratio (reflecting virion maturation) remained significantly lower after drug removal. Amprenavir effectively blocks HIV‑1 replication in this important reservoir and exerts lasting effects, suggesting protease inhibitors may help prevent viral dissemination from macrophage reservoirs.

Fig. 1 Kinetics of human immunodeficiency virus 1 (HIV-1) p24 gag Ag production in supernatants from HIV-1 chronically-infected monocyte-derived macrophages (MDM) treated with different doses of amprenavir (AMP). (Borrajo A, et al., 2017)

Through molecular docking of 147 drugs and subsequent molecular dynamics simulations, three candidates were identified that destabilize the spike protein‑ACE2 interaction. Binding energies of spike with ACE2 were: alone –29.58 kcal/mol; with amprenavir –20.13; with enalaprilat –23.84; with plerixafor –19.72 kcal/mol. Plerixafor showed the greatest destabilizing potential, followed by amprenavir and enalaprilat. These drugs may prevent viral entry by weakening the complex, warranting in vitro and in vivo evaluation as COVID‑19 treatments.

Fig. 2 Amprenavir-spike protein-angiotensin-converting enzyme 2 (Amp-SP-ACE2) complex. (Buitrón-González I, et al., 2021)