Scientists have designed a Protein that block HIV Strains
A novel drug candidate against HIV
has been created by a joint team led by researchers at The Scripps Research
Institute in Jupiter, FL. The scientists consider it to be so potent and
effective that it could form the basis of a vaccine alternative.
The scientists designed a protein that simultaneously binds to two sites on the surface of the virus, which blocks it from entering a host cell. |
"Our compound is the broadest and most effective entry inhibitor described so far," says Michael
Farzan, a Scripps Research Institute professor who led the effort.
"Unlike antibodies, which fail to neutralize a
large fraction of HIV-1 strains," continues Farzan, "our protein has
been effective against all strains tested; raising the possibility it could
offer an effective HIV vaccine
alternative."
Farzan claims that the project is the culmination of more than a
decade's work on the biochemistry of how HIV enters cells.
The results of the study, which are published in the journal Nature,
demonstrate how the new drug candidate blocked every strain of HIV-1, HIV-2 and
SIV (simian immunodeficiency virus), including the variants that are most
difficult to block.
The new drug was also found to protect against doses of the
virus higher than those that normally occur in human transmission for at least
8 months after injection.
New protein was engineered following previous research on the CCR5 co-receptor
When a cell is infected by HIV, it inserts its own
single-stranded RNA into the host cell. This insert of genetic code allows the
virus to transform the cell into a "manufacturing site" for HIV.
However, the Scripps researchers had previously investigated a
co-receptor - CCR5 - that could be used to prevent infection by manipulating
related proteins. CCR5 is the first "anchor point" on the surface of
a cell that HIV binds to before it can penetrate the cell.
"When we did our original work on CCR5, people thought it
was interesting, but no one saw the therapeutic potential," says Farzan.
"That potential is starting to be realized."
Using the CCR5 work as a point of departure, the scientists
designed a protein that mimics the receptor and simultaneously binds to two
sites on the surface of the virus, which prevents it from entering a host cell.
Study first author Matthew Gardner explains how the protein
prevents the virus from penetrating cells:
"When antibodies try to
mimic the receptor, they touch a lot of other parts of the viral envelope that
HIV can change with ease. We've developed a direct mimic of the receptors
without providing many avenues that the virus can use to escape, so we catch
every virus thus far."
A delivery mechanism for the drug
candidate was designed using an engineered adeno-associated virus. This is a
small, relatively harmless virus that does not cause disease. The
adeno-associated virus turns cells into manufacturing sites that churn out
enough of the new protective protein to potentially last for decades.
The data published by the team
shows that the new drug candidate binds more strongly to the HIV-1 envelope
than the best neutralizing antibodies currently known to work against the
virus. Although it will be years before the protein can be tested in humans, it
has been successful against SIV in a macaque model.
Recently, we looked at news that
a recombinant strain of HIV exhibiting unprecedented aggression has been identified
in Cuba.
Scientists researching this new
HIV strain found that, after binding to CCR5, the virus moves to the next
co-receptor - CXCR4 - much more quickly than other HIV strains. The move of the
virus to CXCR4 is typically associated with onset of AIDS symptoms.
While this transition from CCR5
to CXCR4 is normally very difficult, the recombinant HIV variant was found to
contain a protease that makes this transition easier to occur and also enables
the virus to replicate in greater numbers than usual.
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