Hepatitis E virus (HBV) is one of the world's leading causes of liver cancer. There is an urgent need for HBV therapeutics, since current strategies are of limited clinical value. We have identified and synthesized which peptides prevent HIV infection via their affinity for the HIV glycoprotein gp41, and are being developed for therapeutic use. Also, we have demonstrated in vitro selective peptide inhibitors of respiratory syncytial virus (RSV), human parainfluenza virus type 3 (HPIV- 3), and measles virus (MeV). Analogous to the HIV gp41 protein, these viruses have fusion (F) protein which are required for infection.The peptides were effective in the nano and micromolar range, presumably working at extracellular locations. Structural similarities to the gp41 site were identified in HBV preS protein, using Trimeris' computerized antifusion search technology. The project aims are to synthesize and test, in a unique tissue culture HBV infectivity assay described by our academic collaborators, peptides derived from 1) identified regions of the HBV envelope; and 2) an M13 phage display library. The overall goal of this proposal is to produce synthetic peptides derived from the preS protein of HBV having structural or functional properties that make them useful as antiviral agents.Proposed commercial application:Peptides and peptidomimetics that inhibit HBV infection will be identified. Such compounds will be commercialized for sale and used as therapy for chronic and acute HBV infection if appropriate efficacy studies are satisfactory.National Institute of Allergy and Infectious Diseases (NIAID)
