Methods for Production of a Solution Assay and High-Throughput Screen to Probe the Interaction Between the Human Cullin-RING Ligase Complex and the HIV-1 Protein on a Muti-Milligram Scale

 Brief Description:

HIV-1 infection leads to the expression of the viral Vif protein which is essential to evade the host’s own A3G and A3F defense factors. Vif works in concert with the cell’s own ubiquitin ligase machinery to promote degradation of A3G and A3F. This requires a direct interaction between Vif and the human proteins Elongin B, C (EloB/C) and Cullin 5 (Cul5).

 

This invention can be broken into two parts:

1. A method to produce pure, soluble and biologically active HIV-1 Vif protein and the human proteins Elongin B, C (EloB/C) and Cullin 5 (Cul5) in large quantity.

2. The development of a high-throughput screening (HTS) assay aimed at identifying first-in-class antiviral compounds.

 

Applications:

A HTS assay for the identification of novel compounds that block the interaction between Cul5 and the HIV-1 Vif protein. New compounds will be discovered that will protect the infected cell’s own innate immune factors, A3G and A3F.

Advantages:

This is a novel anti-viral mechanism and an assay to screen for compounds that would activate an infected cell’s own immune response, providing an alternative strategy to treating the HIV-1 infection. This approach can be used in combination with the present standard of care therapies and does not carry with it the resistance issues associated with the present HIV antivirals.

 

URV Reference Number: 6-1875
Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Matan Rapoport
Licensing Associate
University of Rochester
585.276.6600
matan.rapoport@rochester.edu
Inventors:
Jason Salter
Joseph Wedekind
Harold Smith
Keywords:
AIDS
Antiviral
Combinatorial Chemistry
Drug Design
HIV
HTS
Infection
Infectious Disease
Target Validation
Therapy
Viral disease