Synthetic Peptide Libraries For Antiviral Drug Discovery

Infections with herpes simplex viruses type-1 and type-2 are a major health problem in the U.S.with over 500,000 new cases per year. New drugs to treat herpes infections are needed, particularlysince the virus is known to develop resistance to nucleoside analogs. Peptides have been shown toblock the entry of viruses into the host cell, the activity of essential viral encoded enzymes andpotentially other processes in the life cycle of viruses. A Synthetic Peptide Combinatorial Library (SPCL)composed of over 52 million D-amino acid hexapeptides will be screened for antiviral activity againstherpes simples virus type-1. This unique drug discovery approach utilizes an iterative selection processto identify individual defined peptides for further efficacy studies. When the 400 samples of a D-aminoacid hexapeptide library were screened, 22% of the mixtures were found to be active. Preliminaryexperiments have revealed D-amino acid peptide mixtures which inhibit the virus after infection of thehost cell. D-amino acid peptides are expected to resist proteolytic degradation more effectively and;therefore, they will have greater efficacy in vivo as topically active antiviral therapeutic agents.