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Elucidating the mechanism of action of cyclotides: ultra-stable proteins from plants

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Can plant extracts help prevent HIV infection?

A microbicidal gel made from plant extracts could help protect future generations from contracting HIV during sexual intercourse. Cyclotides, the gel's magic ingredient, seek out and destroy the membranes of the HIV virus.

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The 'Elucidating the mechanism of action of cyclotides: ultra-stable proteins from plants' (Cyclotide Mechanism) project is investigating the bioactivity of cyclotides. Cyclotides are a family of proteins produced by plants that have a special knot-like structure. With initial research indicating their potential as anti-viral agents, the Cyclotide Mechanism project presented opportunity for further in-depth investigation. Specific insight into the interaction between cyclotides and cellular membranes has been gained through analyses using different types of spectroscopy. Project members learned that bioactivity is regulated by the lipid composition of the membrane. In fact, tests on different types of cells revealed particularly high activity for human immunodeficiency virus (HIV) particles; the cyclotides literally destroyed the membrane of the virus. Excited by the prospect of anti-HIV properties, Cyclotide Mechanism delved even further into cyclotide structure. It turns out cyclotides are not only extremely stable but can also withstand substitution, which makes them an attractive candidate for treatment since toxicity can be reduced. Results thus far have led to the conclusion that a microbicidal gel applied prior to sexual intercourse is likely an ideal way to deliver the cyclotides' anti-HIV effect. The knowledge obtained during Cyclotide Mechanism will be indispensable when it comes time to design anti-HIV drugs based on cyclotides.

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