Therapeutics to prevent HIV-associated Coronary Artery Disease

Case ID: 016-022-Bukrinsky

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.


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


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

Patent Information:

Title App Type Country Patent No. File Date Issued Date Patent Status
Compounds inhibiting Nef-calnexin interaction Nationalized PCT *United States of America 10,684,274 7/11/2018 6/16/2020 Issued
Compounds inhibiting Nef-calnexin interaction Divisional *United States of America 11,131,661 4/6/2020 9/28/2021 Issued
Compounds inhibiting Nef-calnexin interaction Divisional *United States of America   8/24/2021   Filed

For Information, Contact:

Brian Coblitz
Sr. Licensing Manager
George Washington University


Michael Bukrinsky
Ruth Hunegnaw
Alexei Adzhubei