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Therapeutics to prevent HIV-associated Coronary Artery Disease

Technology #016-022-bukrinsky-nef-inhibitor

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Researchers
Michael Bukrinsky
Alexei Adzhubei
Ruth Hunegnaw
Managed By
Brian Coblitz
Sr. Licensing Associate coblitz@gwu.edu (202) 994-4345
Patent Protection

Compounds inhibiting Nef-calnexin interaction

US Patent Pending PCT/US2017/013236
Publications
Interaction Between HIV-1 Nef and Calnexin: From Modeling to Small Molecule Inhibitors Reversing HIV-Induced Lipid Accumulation
Arterioscler Thromb Vasc Biol, 2016 Sep;36(9):1758-71

HIV-infected patients have high risk of coronary artery disease (CAD). Previously, GW researchers identified HIV regulatory protein Nef as a causative factor in foam cell formation, a precursor condition to CAD. Currently, GW researchers developed compounds that show Nef-neutralizing effects in vitro. The prototype compounds restore cholesterol efflux from HIV-infected cells and prevent HIV-induced inhibition of ATP-binding cassette transporter (ABCA-1) activity.

Inhibition of Nef-calnexin interaction disrupts the ability of HIV-1 Nef to downregulate ABCA-1 and block ABCA-1 dependent cholesterol efflux, which are the mechanisms behind Nef-mediated hypoalphalipoproteinemia and atherosclerosis in HIV-infected individuals.

The technology identifies potential targets that can be exploited to block the pathogenic effect of HIV infection on cholesterol metabolism by characterizing important structural features of the Nef/calnexin interaction and identifying a small molecule compound that blocks this interaction and reverses negative effects of HIV infection on cellular cholesterol metabolism. At present, data has been tested in HIV-infected cells in culture with plans to test the prototype compounds in animal models of HIV infection.
 

Applications: 

·  Small molecule therapeutics to prevent or treat HIV-associated atherosclerosis

Advantages: 

· First treatment to target cause of HIV-associated atherosclerosis rather than trying to just lower lipids by standard methods