Human immunodeficiency virus type 1 protease (HIV-1 PR) and renin are primary 
targets toward AIDS and hypertension therapies, respectively. Molecular 
mechanics Poisson-Boltzmann surface area (MM-PBSA) free-energy calculations and 
inhibition assays for canagliflozin, an antidiabetic agent verified its 
effective binding to both proteins (ΔG(pred) = -9.1 kcal mol(-1) for 
canagliflozin-renin; K(i,exp)= 628 nM for canagliflozin-HIV-1 PR). Moreover, 
drugs aliskiren (a renin inhibitor) and darunavir (an HIV-1 PR inhibitor) showed 
high affinity for HIV-1 PR (K(i,exp)= 76.5 nM) and renin (K(i,pred)= 261 nM), 
respectively. Importantly, a high correlation was observed between experimental 
and predicted binding energies (r(2) = 0.92). This study suggests that 
canagliflozin, aliskiren, and darunavir may induce profound effects toward dual 
HIV-1 PR and renin inhibition. Since patients on highly active antiretroviral 
therapy (HAART) have a high risk of developing hypertension and diabetes, 
aliskiren-based or canagliflozin-based drug design against HIV-1 PR may 
eliminate these side-effects and also facilitate AIDS therapy.