- 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.
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- 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.
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- 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.
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- 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."
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- Also at stake are the lives of HIV/AIDS patients living
in countries where expensive AIDS drugs aren't readily available.
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- Tailor-made to Attach
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- 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.
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- 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.
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- 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.
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- The researchers designed 5-Helix to bind to gp41 and
prevent its harpoon attack.
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- Drug Applications
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- 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.
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- But before the researchers can develop a drug, they have
to travel a long road of animal, and eventually human, trials.
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- 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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