Science

HCV peptide C5A has potent antiviral activity against HCV and HIV

Last Updated: 2008-04-02 14:44:16 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - A synthetic peptide derived from a hepatitis C virus (HCV) protein - dubbed "C5A" -- has a unique virucidal mode of action with potent activity that renders HIV and HCV particles noninfectious, according to new research.

"C5A appears to represent the prototype of a new generation of antiviral agents that may have promise for the prevention and treatment of HIV," Dr. Francis V. Chisari, at The Scripps Research Institute in La Jolla, California, and colleagues report in the PNAS Early Edition posted online April 1.

C5A is an alpha-helical peptide with both hydrophilic and lipophilic regions that is derived from the HCV non-structural 5A membrane anchor domain.

"We originally discovered C5A by screening a synthetic peptide library consisting of an overlapping series of (polymers) for antiviral activity against HCV," Dr. Chisari told Reuters Health.

"I think the synthetic C5A peptide is virucidal for HCV and HIV by inserting its rigid corkscrew-type structure into the outer leaflet of the lipid bilayer of the envelopes of both viruses and, by torsional stress, essentially shredding them," the scientist explained. "Without an intact envelope, both HCV and HIV are not infectious."

They found that C5A prevents infection of macrophages, dendritic cells, and CD4+ T lymphocytes "by multiple HIV clade representatives and multidrug-resistant viruses." In addition to its ability to block transmission of HIV by dendritic cells and transmigration across primary genital epithelial cells, C5A can also abrogate an ongoing T cell infection.

C5A is nontoxic in rodents at concentrations up to 200 times higher than the concentration required for antiviral activity in vitro.

"We are particularly intrigued by the opportunities created by C5A's entirely unique mechanism of action," Dr. Chisari said. "By destroying HCV and HIV particles outside the cell, C5A should prevent viral spread to uninfected cells."

"Because C5A targets the viral lipid membrane, viruses can't escape from its antiviral activity the way they do from all the other antiviral agents that are in use for HIV and under development for HCV," he continued. "Therefore, C5A could be combined with any of the 'conventional' antivirals to prevent the spread of viruses that become resistant to those drugs."

With its ability to destroy virus on contact, C5A may also be uniquely effective as a microbicide to prevent sexual transmission of HIV and HCV, he added.

"I have formed a company (Viriome, Inc) that has licensed C5A from the Scripps Research Institute," Dr. Chisari said. "Viriome is carrying out the preclinical analysis of C5A, and is currently seeking a partner in the pharmaceutical industry to advance it to the clinic."

Proc Natl Acad Sci USA 2008.