title: Peptide inhibitors of viral assembly: a novel route to broad-spectrum antivirals.
abstract: We investigated the potential of small peptide segments to function as broad-spectrum antiviral drug leads. We extracted the α-helical peptide segments that share common secondary-structure environments in the capsid protein-protein interfaces of three unrelated virus classes (PRD1-like, HK97-like, and BTV-like) that encompass different levels of pathogenicity to humans, animals, and plants. The potential for the binding of these peptides to the individual capsid proteins was then investigated using blind docking simulations. Most of the extracted α-helical peptides were found to interact favorably with one or more of the protein-protein interfaces within the capsid in all three classes of virus. Moreover, binding of these peptides to the interface regions was found to block one or more of the putative "hot spot" regions on the protein interface, thereby providing the potential to disrupt virus capsid assembly via competitive interaction with other capsid proteins. In particular, binding of the GDFNALSN peptide was found to block interface "hot spot" regions in most of the viruses, providing a potential lead for broad-spectrum antiviral drug therapy.
authors.affiliation: York Centre for Complex Systems Analysis (YCCSA), University of York, York YO10 5YW, UK.
authors.forename: Karim M
authors.initials: KM
authors.lastname: ElSawy
authors.forename: Reidun
authors.initials: R
authors.lastname: Twarock
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Verma
authors.forename: Leo S D
authors.initials: LS
authors.lastname: Caves
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism; D055808:Drug Discovery; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D013045:Species Specificity; D019065:Virus Assembly / Q000187:drug effects*; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D009842:Oligopeptides; D010446:Peptide Fragments