title: Combination effects of peramivir and favipiravir against oseltamivir-resistant 2009 pandemic influenza A(H1N1) infection in mice.
abstract: Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Sehee
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Jin Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Ilseob
authors.initials: I
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Sangmoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Min-Woong
authors.initials: MW
authors.lastname: Hwang
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Joon-Yong
authors.initials: JY
authors.lastname: Bae
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Heo
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Donghwan
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Seok-Il
authors.initials: SI
authors.lastname: Jang
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Infectious Diseases, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Cheong
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Song
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea.
authors.forename: Ki-Joon
authors.initials: KJ
authors.lastname: Song
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea.
authors.forename: Luck Ju
authors.initials: LJ
authors.lastname: Baek
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Man-Seong
authors.initials: MS
authors.lastname: Park
mesh_terms: D000146:Acids, Carbocyclic; D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D024882:Drug Resistance, Viral / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D008168:Lung / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008811:Mice, Inbred DBA; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000401:mortality; D053139:Oseltamivir / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D000146:Acids, Carbocyclic; D000577:Amides; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D011719:Pyrazines; D053139:Oseltamivir; C462182:favipiravir; C414210:peramivir