title: The in vitro and in vivo antiviral properties of combined monoterpene alcohols against West Nile virus infection.
abstract: West Nile Virus (WNV) is a mosquito-borne flavivirus that can cause neuroinvasive disease in humans and animals for which no therapies are currently available. We studied an established combination of monoterpene alcohols (CMA) derived from Melaleuca alternifolia, against WNV infection. The in vitro results show that CMA exhibits virucidal activity, as well as reduces the viral titres and percentage of infected cells. The antiviral mechanism of action of CMA was studied. We found that CMA did not alter the intracellular pH, neither induced apoptosis, but did induce cell cycle arrest in the G0/G1-phase although that was not the antiviral mechanism. Furthermore, we tested CMA in vivo using IRF 3(-)(/)(-)/7(-/-)mice and it was found that CMA treatment significantly delayed morbidity due to WNV infection, reduced the loss of body weight and reduced the viral titres in brain. These findings suggest that CMA could be a therapeutic agent against WNV infection.
authors.affiliation: School of Medical Sciences, Molecular Basis of Disease, Griffith University, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, Australia. Electronic address: adriana.pliego-zamora@griffithuni.edu.au.
authors.forename: Adriana
authors.initials: A
authors.lastname: Pliego Zamora
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, Australia.
authors.forename: Judith H
authors.initials: JH
authors.lastname: Edmonds
authors.affiliation: Centre for Environment and Population Health, Griffith University, Queensland, Australia.
authors.forename: Maxwell J
authors.initials: MJ
authors.lastname: Reynolds
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, Australia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
authors.affiliation: School of Medical Sciences, Molecular Basis of Disease, Griffith University, Queensland, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ralph
mesh_terms: D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018345:Mice, Knockout; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D014901:West Nile Fever / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000821:virology*; D014902:West Nile virus / Q000187:drug effects* / Q000502:physiology
chemical_list: D000438:Alcohols; D000998:Antiviral Agents; D039821:Monoterpenes
keywords: Antiviral agent; Cell cycle; Flavivirus; Mice; Virucidal