Screening method for the identification of compounds capable of abrogation HIV-1 gag-cyclophilin complex formation

US5773225A · kind A · utility

Assignee

• The Trustees of Columbia University in the City of New York · US

Inventors

• Jeremy Luban · New York, US
• Stephen P. Goff · Orefield, US

Key dates

• Filing date: May 24, 1994
• Grant date: Jun 30, 1998
• Expiry date: May 24, 2014

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N33/56988
• WIPO field: Measurement
• WIPO sector: Instruments

Abstract

The human immunodeficiency virus type 1 (HIV-1) gag gene product is capable of directing the assembly of virion particles independent of other viral elements. The Gag protein also plays an important role during the early stages of viral replication. Employing the yeast two-hybrid system, a cDNA expression library was screened and two host proteins identified. These proteins, designated cyclophilins A and B (CyPsA and B), interacted specifically with the HIV-1 Gag polyprotein Pr55.sup.gag. Glutathione S-transferase-CyP fusion proteins bind tightly to Pr55.sup.gag in vitro. Cyclosporin A (CsA) efficiently disrupts the Gag-CyPA binding interaction. The identification of novel compounds capable of abrogating this protein-protein interaction employing the disclosed screening assay will facilitate the development of HIV-1 antiviral agents.