A p7 ion channel-derived peptide inhibits hepatitis C virus infection in vitro [Microbiology]

August 6th, 2015 by Hong, W., Lang, Y., Li, T., Zeng, Z., Song, Y., Wu, Y., Li, W., Cao, Z.

Viral infection is an early stage of its life cycle and represents a promising target for antiviral drug development. Here, we designed and characterized three peptide inhibitors of HCV infection based on the structural features of the membrane-associated p7 polypeptide of HCV. The three peptides exhibited low toxicity and high stability, while potently inhibited initial HCV infection and suppressed established HCV infection at non-cytotoxic concentrations in vitro. The most efficient peptide (designated H2-3), which is derived from the H2 helical region of HCV p7 ion channel, inhibited HCV infection by inactivating both intracellular and extracellular viral particles. The H2-3 peptide inactivated free HCV with an EC50 (50% effective concentration) of 82.11 nM, which is >1000-fold lower than the CC50 (50% cytotoxic concentration) of Huh7.5.1 cells. H2-3 peptide also bound to cell membrane and protected host cells from viral infection. The peptide H2-3 didn't alter the normal electrophysiological profile of the p7 ion channel or block viral release from Huh7.5.1 cells. Our work highlights a new anti-viral peptide design strategy based on ion channel, giving the possibility that ion channels are potential resources to generate antiviral peptides.