title: Inhibition of influenza virus replication by targeting broad host cell pathways.
abstract: Antivirals that are currently used to treat influenza virus infections target components of the virus which can mutate rapidly. Consequently, there has been an increase in the number of resistant strains to one or many antivirals in recent years. Here we compared the antiviral effects of lysosomotropic alkalinizing agents (LAAs) and calcium modulators (CMs), which interfere with crucial events in the influenza virus replication cycle, against avian, swine, and human viruses of different subtypes in MDCK cells. We observed that treatment with LAAs, CMs, or a combination of both, significantly inhibited viral replication. Moreover, the drugs were effective even when they were administered 8 h after infection. Finally, analysis of the expression of viral acidic polymerase (PA) revealed that both drugs classes interfered with early events in the viral replication cycle. This study demonstrates that targeting broad host cellular pathways can be an efficient strategy to inhibit influenza replication. Furthermore, it provides an interesting avenue for drug development where resistance by the virus might be reduced since the virus is not targeted directly.
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marois
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Cloutier
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.affiliation: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada, and Department of Medical Microbiology, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Hana M
authors.initials: HM
authors.lastname: Weingartl
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: André M
authors.initials: AM
authors.lastname: Cantin
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: Martin V
authors.initials: MV
authors.lastname: Richter
mesh_terms: D000818:Animals; D000863:Antacids / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000472:pathogenicity; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D013552:Swine; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D000863:Antacids; D000998:Antiviral Agents