• The objective of Rigel’s virology program in HIV is to identify new anti-HIV therapeutics by targeting cellular ubiquitin ligase pathways required for HIV replication.


• Rigel has identified compounds that inhibit the function of Vif, a protein produced by HIV that is essential for virus growth. Vif targets Apobec3G, a human cellular protein that possesses potent antiviral activity, for destruction by recruiting Apobec3G to a ubiquitin ligase complex. By neutralizing Vif function and rescuing Apobec3G activity, these compounds are expected to restore the body’s natural ability to fight HIV infection.


• Inhibitors of this class are mechanistically distinct from currently available anti-retroviral therapies and also from drugs in clinical trials, so they may be effective against current drug-resistant HIV strains.


• Rigel is uniquely positioned to pursue this target given our extensive experience in the ubiquitin ligase field and in the virology area.

• Rigel hopes to outsmart HIV in new drug approach

Disease and current treatment approaches
HIV is a virus that targets the immune system, ultimately destroying the cells required by the body to fight infections and certain cancers. For a majority of people, HIV infection is fatal if left untreated, often leading to death from AIDS (acquired immunodeficiency syndrome). Globally, between 33 and 46 million people currently live with HIV. The number of AIDS related deaths in 2006 was close to 2.9 million.

Currently available therapies reduce HIV levels in the body, delaying the time it takes for progression to AIDS, but the virus is not fully eradicated. Due to the mechanism used by the virus for copying its genetic material, its genome is constantly evolving, often enabling the virus to develop resistance to the drugs used to treat HIV infection. As a result, there is a continued need for drugs with new mechanisms of action.

References:

• Navarro F, Landau NR. Recent insights into HIV-1 Vif.
  Curr Opin Immunol. 2004 Aug;16(4):477-82. PMID: 15245742.


• Cullen BR. Role and mechanism of action of the APOBEC3 family of antiretroviral resistance factors.
  J Virol. 2006 Feb;80(3):1067-76. PMID: 16414984