title: Blockage of filoviral glycoprotein processing by use of a protein-based inhibitor.
abstract: Cleavage of the glycoproteins of many virus species by furin and other host cell proteases is required for virus infectivity and, hence, determines viral pathogenicity. Proteolytic processing of Marburg virus and Ebola virus glycoproteins is also mediated by furin; however, for Ebola virus, in contrast to other viruses, glycoprotein cleavage is dispensable for replication in vitro, as has been shown in previous studies. In the present study, by use of a highly potent and selective furin inhibitor, we demonstrate that glycoprotein cleavage inhibition results in a minimal reduction in the virus titer that is insufficient to block filoviral replication. Thus, furin inhibitors are unlikely to be effective in the treatment of filoviral infections.
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Manitoba, Canada R3E 3R2. Ute_Stroeher@phac-aspc.gc.ca
authors.forename: Ute
authors.initials: U
authors.lastname: Ströher
authors.forename: Laura
authors.initials: L
authors.lastname: Willihnganz
authors.forename: François
authors.initials: F
authors.lastname: Jean
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D016563:Filoviridae / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D000882:Haplorhini; D006801:Humans; D015151:Immunoblotting; D007668:Kidney; D029024:Marburgvirus / Q000145:classification / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D012703:Serotyping; D014709:Vero Cells; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D006023:Glycoproteins; D014764:Viral Proteins; D010447:Peptide Hydrolases