Mechanism of an amphipathic alpha-helical peptide's antiviral activity involves size-dependent virus particle lysis.
The N-terminal region of the hepatitis C virus (HCV) nonstructural protein NS5A contains an amphipathic alpha-helix that is necessary and sufficient for NS5A membrane association. A synthetic peptide (AH) comprising this amphipathic helix is able to lyse lipid vesicles that serve as a model system for virus particles. Based on quartz crystal microbalance-dissipation (QCM-D) experiments, the degree of vesicle rupturing was found to be inversely related to vesicle size, with maximal activity in the size range of several medically important viruses. In order to confirm and further study vesicle rupture, dynamic light scattering (DLS) and atomic force microscopy (AFM) experiments were also performed. The size dependence of vesicle rupturing helps explain the peptide's observed effect on the infectivity of a wide range of viruses. Further, in vitro studies demonstrated that AH peptide treatment significantly decreased the infectivity of HCV particles. Thus, the AH peptide might be used to rupture HCV particles extra-corporally (for HCV prevention) and within infected individuals (for HCV therapy).
Cho
Nam-Joon
NJ
Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California 94305, USA.
Dvory-Sobol
Hadas
H
Xiong
Anming
A
Cho
Sang-Joon
SJ
Frank
Curtis W
CW
Glenn
Jeffrey S
JS
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D014771:Virion / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D010455:Peptides; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase