3-D Structure Of HIV Components May Pave The Way For New Anti-AIDS Drugs

N. Borer, professor of chemistry and biophysics at Syracuse University.

Nucleocapsid uses two "zinc knuckles"--special structures that each require a zinc atom to function--to grip the packaging domain on viral RNA. The protein winds the RNA to form the core of new virus particles, which eventually burst forth from an infected cell.

"Dr. Summers had already shown [in a 1993 Nature article and in later publications] that removing the zinc, so that the knuckles fall apart, results in uninfectious viral particles. The particles form, but their genetic material is missing, so they can't spread to other cells," said Dr. Janna Wehrle of the NIGMS Division of Cell Biology and Biophysics.

Pharmaceutical companies took an immediate interest in these previous results, said Dr. Summers. "Nucleocapsid has already been targeted by antiviral agents that eject zinc from the protein, some of which are undergoing clinical tests in the U.S. and U.K.," he said.

Even more effective drugs may be designed specifically to block the molecular embrace between nucleocapsid and RNA. Molecular details of this interaction reveal that the goal is more than theoretical--the viral interaction is completely different from normal interactions in human cells. This indicates that such custom-designed drugs may not only stop viral spread, but also could be safe for patients.

The Summers and Borer groups also have determined the structures of the isolated protein and RNA components. Because HIV and other retroviruses require a nucleocapsid protein to package viral RNA, these structures may not only underlie a new generation of anti-AIDS drugs, but also may accelerate drug development for some types of leukemia and other retroviral diseases.

Other contributors to the work are Roberto N. DeGuzman, Zeng Rong Wu, and Chelsea C. Stalling of UMBC and Lucia Pappalardo of Syracuse University.


Contact: Alisa Zapp Machalek
(301) 496-7301
NIH/National Institute of General Medical Sciences

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