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Scientists increase potency of HIV-battling proteins to help beat disease

The protein, called cyanovirin-N (CV-N), is produced by a type of blue-green algae and can ward off several diseases caused by viruses, including HIV and influenza.

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Scientists increase potency of HIV-battling proteins to help beat disease
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Researchers at the California Institute of Technology (Caltech) have found a relatively simple engineering technique that can boost a small HIV-fighting protein’s prowess.

The protein, called cyanovirin-N (CV-N), is produced by a type of blue-green algae and can ward off several diseases caused by viruses, including HIV and influenza.

“By linking two cyanovirins, we were able to make significantly more potent HIV-fighting molecules,” said Jennifer Keeffe, a staff scientist at Caltech and first author of a new paper describing the study in the Proceedings of the National Academy of Sciences (PNAS).

“One of our linked molecules was 18 times more effective at preventing infection than the naturally occurring, single protein,” added Keeffe.

CV-N binds well to certain carbohydrates, such as the kind found in high quantities connected to the proteins on the envelope that surrounds the HIV virus. Once attached, CV-N prevents a virus from infecting cells, although the mechanism by which it accomplishes this is not well understood.

Each CV-N protein has two binding sites where it can bind to a carbohydrate and that both sites are needed to neutralize HIV.

Once the Caltech researchers had linked two CV-Ns together, they wanted to know if the enhanced ability of their engineered dimers to ward off HIV was related to the availability of additional binding sites. So they engineered another version of the dimers—this time with one or more of the binding sites knocked out—and tested their ability to neutralize HIV.

It turns out that the dimers' infection-fighting potency increased with each additional binding site—three sites are better than two, and four are better than three. The advantages seemed to stop at four sites, however; the researchers did not see additional improvements when they linked three or four CV-N molecules together to create molecules with six to eight binding sites.

Because it is active against multiple disease-causing viruses, including multiple strains of HIV, CV-N holds unique promise for development as a drug therapy.

The study has been published in the Proceedings of the National Academy of Sciences (PNAS).

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