The Journal of infectious diseases · 2018
Combination Therapy With Neuraminidase and Polymerase Inhibitors in Nude Mice Infected With Influenza Virus.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kiso Maki, Lopes Tiago J S, Yamayoshi Seiya, Ito Mutsumi, Yamashita Makoto, Nakajima Noriko, Hasegawa Hideki, Neumann Gabriele, Kawaoka Yoshihiro
Аннотация
BACKGROUND: Treatment of immunocompromised, influenza virus-infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants.
METHODS: Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof.
RESULTS: Combination therapy for 28 days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors.
CONCLUSIONS: Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.
METHODS: Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof.
RESULTS: Combination therapy for 28 days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors.
CONCLUSIONS: Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.
Предметные рубрики MeSH
AmidesAnimalsAntiviral AgentsDose-Response Relationship, DrugDrug Therapy, CombinationEnzyme InhibitorsFemaleGuanidinesImmunocompromised HostInfluenza A Virus, H1N1 SubtypeLungMiceMice, Inbred BALB CMice, NudeNeuraminidaseNucleic Acid Synthesis InhibitorsOrthomyxoviridae InfectionsOseltamivirPyransPyrazinesSialic AcidsZanamivir