title: Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.
abstract: Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin.
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Jonna B
authors.initials: JB
authors.lastname: Westover
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sefing
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Bailey
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA; Utah Veterinary Diagnostic Laboratory, Logan, UT, USA.
authors.forename: Arnaud J
authors.initials: AJ
authors.lastname: Van Wettere
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Kie-Hoon
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Dagley
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Luci
authors.initials: L
authors.lastname: Wandersee
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Brittney
authors.initials: B
authors.lastname: Downs
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.affiliation: Research Laboratories, Toyama Chemical Company, Ltd., Toyama, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Furuta
authors.affiliation: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Bray
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA. Electronic address: brian.gowen@usu.edu.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Gowen
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D018050:Arenavirus / Q000187:drug effects; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003716:Dengue Virus / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D006476:Orthohantavirus / Q000187:drug effects; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000187:drug effects; D006478:Hemorrhagic Fever, American / Q000188:drug therapy; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy; D006482:Hemorrhagic Fevers, Viral / Q000097:blood / Q000188:drug therapy* / Q000662:veterinary / Q000821:virology; D018051:Junin virus / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D051379:Mice; D011719:Pyrazines / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects*; D012254:Ribavirin / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011719:Pyrazines; D012254:Ribavirin; C462182:favipiravir
keywords: Arenavirus; Favipiravir; Junin virus; Ribavirin; Viral hemorrhagic fever