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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

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dc.contributor.author Tzoupis, H en
dc.contributor.author Leonis, G en
dc.contributor.author Megariotis, G en
dc.contributor.author Supuran, CT en
dc.contributor.author Mavromoustakos, T en
dc.contributor.author Papadopoulos, MG en
dc.date.accessioned 2014-03-01T02:08:41Z
dc.date.available 2014-03-01T02:08:41Z
dc.date.issued 2012 en
dc.identifier.issn 00222623 en
dc.identifier.uri http://hdl.handle.net/123456789/29706
dc.subject.other aliskiren en
dc.subject.other canagliflozin en
dc.subject.other darunavir en
dc.subject.other Human immunodeficiency virus proteinase en
dc.subject.other renin en
dc.subject.other acquired immune deficiency syndrome en
dc.subject.other article en
dc.subject.other binding affinity en
dc.subject.other controlled study en
dc.subject.other diabetes mellitus en
dc.subject.other drug binding en
dc.subject.other drug mechanism en
dc.subject.other drug structure en
dc.subject.other enzyme inhibition en
dc.subject.other enzyme structure en
dc.subject.other hypertension en
dc.subject.other molecular docking en
dc.subject.other molecular dynamics en
dc.subject.other prediction en
dc.subject.other Acquired Immunodeficiency Syndrome en
dc.subject.other Diabetes Mellitus en
dc.subject.other HIV Protease en
dc.subject.other HIV Protease Inhibitors en
dc.subject.other HIV-1 en
dc.subject.other Humans en
dc.subject.other Hydrogen Bonding en
dc.subject.other Hypertension en
dc.subject.other Molecular Dynamics Simulation en
dc.subject.other Protein Binding en
dc.subject.other Protein Conformation en
dc.subject.other Renin en
dc.subject.other Sodium-Glucose Transporter 2 en
dc.subject.other Thermodynamics en
dc.title 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 en
heal.type journalArticle en
heal.identifier.primary 10.1021/jm300180r en
heal.identifier.secondary http://dx.doi.org/10.1021/jm300180r en
heal.publicationDate 2012 en
heal.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 (ΔGpred = 9.1 kcal mol-1 for canagliflozin-renin; Ki,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 (Ki,exp= 76.5 nM) and renin (Ki,pred= 261 nM), respectively. Importantly, a high correlation was observed between experimental and predicted binding energies (r2 = 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 American Chemical Society. en
heal.journalName Journal of Medicinal Chemistry en
dc.identifier.doi 10.1021/jm300180r en
dc.identifier.volume 55 en
dc.identifier.issue 12 en
dc.identifier.spage 5784 en
dc.identifier.epage 5796 en


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