New Drug Target Site of HIV Integrase for AIDS Therapy

(REF. NO. 250-MA)


Current HIV/AIDS therapy is not completely curative regardless of how soon after infection it has originated or for how long it has been administered. Therapeutic regiments usually include multiple antiretroviral drugs in attempt to control viral infection. However, therapy interruption often results in revival of viral persistence, which is the major obstacle to complete cure.

Antiretroviral therapy comprises drugs that target viral enzymes important to its life cycle. Viral integrase (IN)is one of enzymes that are essential for retroviral replication and the insertion of viral DNA into the genome of the infected host cell. Therefore, IN is an important target for drugs to treat HIV/AIDS. Nevertheless, the inevitable development of drug resistant viral mutants drives a continuing need for additional strategies to block the activity of this viral enzyme.

Summary of the Invention

In proteins are known to exist as monomers, dimers, and tetramers, where only the tetramer is functionally capable to integrate viral DNA. Using biochemical methods and crystal structures researchers from Fox Chase Cancer Center
have obtained a certain conformations and structural arrangements of retroviral IN protein that are necessary for its proper functionality. These structures are the first, experimentally-derived assemblies of IN mono-and multimers to be reported.
Consequently, the molecular models of HIV-1 IN were constructed. Furthermore,the critical dimer interaction site important for assembly of functional forms of IN have been determined and characterized. This new target site and inhibition of the formation of IN multimers offer a novel route for treatment of retroviral infection. The research kits with IN proteins for screening of small molecules or biological compounds for their capability to inhibit the proper multimerization of retroviral integrases, lead to its dissociation or stabilization of multimers in a conformation that inhibits the biologic activity of enzyme is a powerful tool to develop new drug and therapy to treat HIV/AIDS.


Bojja R.S. et al. Architecture and assembly of HIV integrase multimers in the absence of DNA substrates. J Biol Chem. 2013 Mar 8;288(10):7373-86.

Patent Status:

US Patent # US 9,553,040 B2 issued January 3, 2017