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.

Dual inhibitors for aspartic proteases HIV-1 PR and renin: advancements in AIDS-hypertension-diabetes linkage via molecular dynamics, inhibition assays, and binding free energy calculations / H. Tzoupis;G. Leonis;G. Megariotis;C. T. Supuran;T. Mavromoustakos;M. G. Papadopoulos. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 55:(2012), pp. 5784-5796. [10.1021/jm300180r]

Dual inhibitors for aspartic proteases HIV-1 PR and renin: advancements in AIDS-hypertension-diabetes linkage via molecular dynamics, inhibition assays, and binding free energy calculations.

SUPURAN, CLAUDIU TRANDAFIR;
2012

Abstract

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.
2012
55
5784
5796
H. Tzoupis;G. Leonis;G. Megariotis;C. T. Supuran;T. Mavromoustakos;M. G. Papadopoulos
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/776390
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 36
  • ???jsp.display-item.citation.isi??? 34
social impact