Researchers at Tufts University School of Medicine (Boston, MA) have developed a protein-based inhibitor—using circular dichroism spectroscopy to test its structure and stability—that could lead to a low-cost topical treatment for human papilloma virus (HPV).
Giving patients infected with HPV an alternative to surgical and harsh chemical treatments that destroy affected tissue, the researchers created a protein inhibitor that blocks HPV protein expression in cell culture, focusing on the viral protein E2, which controls viral activities, including DNA replication and the activation of cancer-causing genes. Using structure-guided design, the team developed a protein called E2R that prevents E2 from functioning normally. When the researchers applied E2R to a cell model of HPV biology, viral gene transcription was halted. Because HPV infects epithelial cells, the outermost layer of the skin and the mucous membranes, protein inhibitors such as E2R could be applied in a topical form.
The team then used circular dichroism spectroscopy and x-ray crystallography to test the structure and stability of different inhibitors. The most stable inhibitor was then tested in mammalian cells and was found to inhibit the E2 protein of HPV-16, the high-risk strain that is most commonly associated with cancers. The data in this study suggests that the inhibitor may also be effective against another high-risk virus, HPV-18, as well as a low-risk virus, HPV-6a, which causes warts.
The National Institutes of Health funded this work, which was published online in advance of print in The FASEB Journal.
Posted by Lee Mather
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