Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir

Favipiravir, a viral RNA-dependent RNA polymerase inhibitor, has recently been approved in Japan for influenza pandemic preparedness. Here, we conducted a cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir. In this assay, the antiviral activity of favipira...

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Veröffentlicht in:Antiviral research 2016-08, Vol.132, p.170-177
Hauptverfasser: Takashita, Emi, Ejima, Miho, Ogawa, Rie, Fujisaki, Seiichiro, Neumann, Gabriele, Furuta, Yousuke, Kawaoka, Yoshihiro, Tashiro, Masato, Odagiri, Takato
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container_start_page 170
container_title Antiviral research
container_volume 132
creator Takashita, Emi
Ejima, Miho
Ogawa, Rie
Fujisaki, Seiichiro
Neumann, Gabriele
Furuta, Yousuke
Kawaoka, Yoshihiro
Tashiro, Masato
Odagiri, Takato
description Favipiravir, a viral RNA-dependent RNA polymerase inhibitor, has recently been approved in Japan for influenza pandemic preparedness. Here, we conducted a cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir. In this assay, the antiviral activity of favipiravir is determined by inhibition of virus-induced cytopathic effect, which can be measured by using a colorimetric cell proliferation assay. To demonstrate the robustness of the assay, we compared the favipiravir susceptibilities of neuraminidase (NA) inhibitor-resistant influenza A(H1N1)pdm09, A(H3N2), A(H7N9) and B viruses and their sensitive counterparts. No significant differences in the favipiravir susceptibilities were found between NA inhibitor-resistant and sensitive viruses. We, then, examined the antiviral susceptibility of 57 pairs of influenza viruses isolated from patients pre- and post-administration of favipiravir in phase 3 clinical trials. We found that there were no viruses with statistically significant reduced susceptibility to favipiravir or NA inhibitors, although two of 20 paired A(H1N1)pdm09, one of 17 paired A(H3N2) and one of 20 paired B viruses possessed amino acid substitutions in the RNA-dependent RNA polymerase subunits, PB1, PB2 and PA, after favipiravir administration. This is the first report on the antiviral susceptibility of influenza viruses isolated from patients after favipiravir treatment. •A cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir were conducted.•No significant differences in favipiravir susceptibilities were found between NA inhibitor-resistant and sensitive viruses.•Favipiravir administration did not affect the susceptibility of influenza viruses to favipiravir and NA inhibitors.
doi_str_mv 10.1016/j.antiviral.2016.06.007
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subjects Amides - pharmacology
Amides - therapeutic use
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Antiviral resistance
Cell Line
Cells, Cultured
Cytopathogenic Effect, Viral - drug effects
Dose-Response Relationship, Drug
Drug Resistance, Viral
Favipiravir
Humans
Influenza
Influenza A virus - drug effects
Influenza A virus - isolation & purification
Influenza, Human - drug therapy
Influenza, Human - virology
Microbial Sensitivity Tests
Neuraminidase - antagonists & inhibitors
Orthomyxoviridae - drug effects
Orthomyxoviridae - isolation & purification
Polymerase inhibitor
Pyrazines - pharmacology
Pyrazines - therapeutic use
T-705
Viral Proteins - antagonists & inhibitors
title Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir
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