Chemical compounds that bind to both CCR5 and CXCR4 chemokine GPCRs as therapeutics to block HIV entry and infection.
- Targets both chemokine receptors used for cell entry by HIV: CCR5 & CXCR4.
- Eliminates the requirement of a tropism pre-test used for drug administration of single chemokine agents.
- Does not interfere with CXCR4-based G-protein coupled receptor signaling, suggesting they may be HIV-chemokine selective and reduce toxic side effects.
- May provide better drug resistance profile versus other HIV medications.
More than 1.2 million people in the United States are living with HIV infection with about 50,000 new HIV cases each year. Highly active antiretroviral therapy (HAART) has limited HIV infection in developed countries and normally includes several antiretroviral agents that act on different stages of the HIV life-cycle. Combinations of antiretroviral agents form multiple obstacles to HIV replication to keep the viral load low and reduce the possibility of a superior mutation. However, due to the short life cycle and high error rate, HIV still generates drug-resistant strains in patients who do not take their regimen regularly, creating the need for new anti-HIV drugs. There are currently only two FDA-approved HIV entry inhibitors and neither inhibitor targets CXCR4.Ã‚ Furthermore, as the CXCR4-using variant of the virus highly correlates to the development of AIDS, an agent that targets this mechanism is an urgent and unmet need.
Emory University researchers have identified compounds which potentially bind to both CCR5 and CXCR4 chemokine receptors. Initial results for some of the lead compounds show they do not interfere with CXCR4-based G-protein (GPCR) mediated signaling and therefore may have reduced toxic side effects. There are several lead compound series that have shown activity against both tropic forms of the virus in vitro. This technology may lead to anti-HIV drugs with lower resistance profiles.
Lead compounds have been identified and experiments are planned to improve anti-viral potency as well as performing further mechanistic studies.