Alliance Identifies New Class of Agents With Potential to Treat HIV/AIDS

Researchers from the University of Maryland-Baltimore County and Achillion Pharmaceuticals announced the discovery of a new target on the HIV molecule that could lead to a new class of antiviral drugs to fight HIV/AIDS.

"The greatest challenge in treating HIV today is drug resistance brought on when the virus mutates and renders existing drugs ineffective at stopping viral replication," said study author Michael Summers, UMBC professor of chemistry/biochemistry and Howard Hughes Medical Institute investigator. "Our research has led to the identification of a new class of compounds that inhibit a novel target in HIV. These compounds disrupt the assembly of the HIV-1 capsid protein, which is a vital step in changing immature, non-infectious HIV into its mature, infectious form."

According to Achillion CEO William G. Rice, Ph.D., researchers have long been looking at the HIV-1 capsid protein as a potential drug target. "While we are encouraged by the laboratory tests of the compounds we've identified so far, additional testing needs to be undertaken before this approach can be tested in humans," said Rice.

The target was identified by Summers and his team at the UMBC HHMI laboratory. They discovered a number of compounds that bound to a specific area of the capsid protein thought to play a key role in the assembly process necessary for HIV to mature to its infectious form. Once computer models identified the new capsid assembly target and compounds inhibiting the target, researchers from privately held Achillion tested the compounds in a number of biochemical assays, as well as in human cells infected with live HIV. This demonstrated that the anti-HIV activity of inhibitors was indeed due to the disruption of the HIV-1 capsid protein.

Three patents have now been filed based on the study findings. "These findings offer exciting opportunities for the discovery of new drugs to treat HIV," Rice said. "These compounds are part of the portfolio of drug candidates we are building to treat infectious diseases, including antiviral drugs to treat hepatitis B and C and HIV. Achillion will continue to collaborate with Summers' team to identify additional candidates for optimization and clinical testing."

The study, "Antiviral Inhibition of the HIV-1 Capsid Protein," was published in the April 11th edition of the Journal of Molecular Biology (2003;327(5):1013-1020).

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