Designer protein 'blocks all known strains of HIV'

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.

"Our compound is the broadest and most potent 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: 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.