Development of interferon mimetic peptides having antiviral activity

Abstract

Abstract Current treatment options are limited for ameliorating viral infections. Interferons are involved in immune responses to viral infections; however, these interferons are not induced by some viral infections and, furthermore, can have toxic side effect when given at high doses as a therapeutic. The objective of this research is to design peptide mimetics of interferons that are not toxic to cells but have antiviral activities similar to interferons. Eleven peptides were designed based on interferon sequences and their receptor binding sites. Their activity on cell proliferation, toxicity, and antiviral effects against vesicular stomatitis virus (VSV) challenge of HeLa cells were measured. Results show that none of the peptides had significant antiviral activity when peptides were preincubated or incubated at the same time with the cells before VSV challenge. However, one peptide (Bact2) did have antiviral activity at 60ug/mL when this peptide was preincubated with the VSV virus for 24 hours before the HeLa cells were added to the mixture, suggesting that the Bact2 peptide directly bound to the VSV virus for its antiviral effect. Further analysis of the toxicity of the Bact2 peptide incubated alone with HeLa cells showed no cellular toxicity at concentrations of 60ug/mL or lower. Thus, the results from this study show that short peptides could be developed to directly neutralize viruses and interfere with their infectivity of cells.