New Protein Prevents HIV
From Getting Into Cells
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CHEVY CHASE, MARYLAND - Scientists have designed a protein called 5-Helix that can stop HIV from infecting human cells. The theory goes that if the virus can't get in to cells, it can't replicate and cause disease.
The protein works by binding to a region of the coat protein of HIV. Once 5-Helix is bound to the virus, HIV can't fuse with the membranes of the cells it's trying to infect.
Researchers say such 'entry inhibitors' represent a promising alternative line of attack against HIV. Currently used drugs target HIV at other points during its life cycle - after the virus has already infected the patient's cells.
Sometimes these drugs fail because the virus is mutating to form variants which escape treatment. Dr. Peter Kim at the Howard Hughes Medical Institute says, "Current therapy is working, but sexual transmission of virus that is resistant to treatment has been documented, making it important to continue to find new targets and therapies for stopping HIV."
Also at stake are the lives of HIV/AIDS patients living in countries where expensive AIDS drugs aren't readily available.
Tailor-made to Attach
The 5-Helix protein was designed with the HIV coat protein in mind. Decades of research have been devoted to decoding the structure of the HIV coat protein - called gp41.
Two years ago, its architecture was described by Kim's lab. This protein plays a key role in allowing the virus membrane to fuse with the membrane of the cell it's attacking.
In its inactive form, gp41 lies just below the surface of the virus coat. As HIV prepares to enter a cell, it undergoes a change. A dormant protein region is propelled, harpoon-like, toward the host cell membrane, hooking the target for infection.
The researchers designed 5-Helix to bind to gp41 and prevent its harpoon attack.
Drug Applications
According to Kim's team, the designer protein is a good candidate to be used in a drug. It's very stable, so it's less likely to be degraded by the body's enzymes; can be made larger to avoid being eliminated by the kidneys; and can be modified so it can escape the body's immune response.
But before the researchers can develop a drug, they have to travel a long road of animal, and eventually human, trials.
Results from the 5-Helix study are published in the January 11 issue of ScienceExpress (an electronic publication of Science magazine highlighting papers from future issues).

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