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...
Gespeichert in:
Veröffentlicht in: | Antiviral research 2016-08, Vol.132, p.170-177 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 177 |
---|---|
container_issue | |
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 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1815701040</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0166354216303382</els_id><sourcerecordid>1810559790</sourcerecordid><originalsourceid>FETCH-LOGICAL-c519t-6713e4ab19032d7afe606b30d2949f6817e2f379a7869f540bc26f44d03578473</originalsourceid><addsrcrecordid>eNqNkUFr3DAQhUVJaTZp_0KjYy7ejmRbso5LaNJAoJf2LGRrBFpsy5HkhfTXV2aTXFsYEGg-vTeaR8gNgz0DJr4d92bO_uSjGfe8XOyhFMgPZMc6ySsFSlyQXWmIqm4bfkmuUjoCgJCq-0Quuax56bU7shzedGha04BL9r0ffX6hwVE_u3HF-Y-hhVgTJupTGE1GS10ME11M9jjnRJeIFTWzpUtIuTJ28rNPOZZ2mDchZ05-KSZF5jP56MyY8MvreU1-33__dfejevr58Hh3eKqGlqlcCclqbEzPFNTcSuNQgOhrsFw1yomOSeSulsrITijXNtAPXLimsVC3smtkfU1uz7pLDM8rpqwnX_43jmbGsCbNOtZKYNDA_6DQtkqqDZVndIghpYhOL9FPJr5oBnpLRh_1ezJ6S0ZDKdjm-fpqsvYT2vd3b1EU4HAGsGzl5DHqNJTtDmh9xCFrG_w_Tf4C1GalQg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1810559790</pqid></control><display><type>article</type><title>Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir</title><source>Elsevier ScienceDirect Journals Complete - AutoHoldings</source><source>MEDLINE</source><creator>Takashita, Emi ; Ejima, Miho ; Ogawa, Rie ; Fujisaki, Seiichiro ; Neumann, Gabriele ; Furuta, Yousuke ; Kawaoka, Yoshihiro ; Tashiro, Masato ; Odagiri, Takato</creator><creatorcontrib>Takashita, Emi ; Ejima, Miho ; Ogawa, Rie ; Fujisaki, Seiichiro ; Neumann, Gabriele ; Furuta, Yousuke ; Kawaoka, Yoshihiro ; Tashiro, Masato ; Odagiri, Takato</creatorcontrib><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.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2016.06.007</identifier><identifier>PMID: 27321665</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>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</subject><ispartof>Antiviral research, 2016-08, Vol.132, p.170-177</ispartof><rights>2016 The Authors</rights><rights>Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-6713e4ab19032d7afe606b30d2949f6817e2f379a7869f540bc26f44d03578473</citedby><cites>FETCH-LOGICAL-c519t-6713e4ab19032d7afe606b30d2949f6817e2f379a7869f540bc26f44d03578473</cites><orcidid>0000-0002-9064-4699</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.antiviral.2016.06.007$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27321665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takashita, Emi</creatorcontrib><creatorcontrib>Ejima, Miho</creatorcontrib><creatorcontrib>Ogawa, Rie</creatorcontrib><creatorcontrib>Fujisaki, Seiichiro</creatorcontrib><creatorcontrib>Neumann, Gabriele</creatorcontrib><creatorcontrib>Furuta, Yousuke</creatorcontrib><creatorcontrib>Kawaoka, Yoshihiro</creatorcontrib><creatorcontrib>Tashiro, Masato</creatorcontrib><creatorcontrib>Odagiri, Takato</creatorcontrib><title>Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><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.</description><subject>Amides - pharmacology</subject><subject>Amides - therapeutic use</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral resistance</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>Cytopathogenic Effect, Viral - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Resistance, Viral</subject><subject>Favipiravir</subject><subject>Humans</subject><subject>Influenza</subject><subject>Influenza A virus - drug effects</subject><subject>Influenza A virus - isolation & purification</subject><subject>Influenza, Human - drug therapy</subject><subject>Influenza, Human - virology</subject><subject>Microbial Sensitivity Tests</subject><subject>Neuraminidase - antagonists & inhibitors</subject><subject>Orthomyxoviridae - drug effects</subject><subject>Orthomyxoviridae - isolation & purification</subject><subject>Polymerase inhibitor</subject><subject>Pyrazines - pharmacology</subject><subject>Pyrazines - therapeutic use</subject><subject>T-705</subject><subject>Viral Proteins - antagonists & inhibitors</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFr3DAQhUVJaTZp_0KjYy7ejmRbso5LaNJAoJf2LGRrBFpsy5HkhfTXV2aTXFsYEGg-vTeaR8gNgz0DJr4d92bO_uSjGfe8XOyhFMgPZMc6ySsFSlyQXWmIqm4bfkmuUjoCgJCq-0Quuax56bU7shzedGha04BL9r0ffX6hwVE_u3HF-Y-hhVgTJupTGE1GS10ME11M9jjnRJeIFTWzpUtIuTJ28rNPOZZ2mDchZ05-KSZF5jP56MyY8MvreU1-33__dfejevr58Hh3eKqGlqlcCclqbEzPFNTcSuNQgOhrsFw1yomOSeSulsrITijXNtAPXLimsVC3smtkfU1uz7pLDM8rpqwnX_43jmbGsCbNOtZKYNDA_6DQtkqqDZVndIghpYhOL9FPJr5oBnpLRh_1ezJ6S0ZDKdjm-fpqsvYT2vd3b1EU4HAGsGzl5DHqNJTtDmh9xCFrG_w_Tf4C1GalQg</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Takashita, Emi</creator><creator>Ejima, Miho</creator><creator>Ogawa, Rie</creator><creator>Fujisaki, Seiichiro</creator><creator>Neumann, Gabriele</creator><creator>Furuta, Yousuke</creator><creator>Kawaoka, Yoshihiro</creator><creator>Tashiro, Masato</creator><creator>Odagiri, Takato</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0002-9064-4699</orcidid></search><sort><creationdate>201608</creationdate><title>Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir</title><author>Takashita, Emi ; Ejima, Miho ; Ogawa, Rie ; Fujisaki, Seiichiro ; Neumann, Gabriele ; Furuta, Yousuke ; Kawaoka, Yoshihiro ; Tashiro, Masato ; Odagiri, Takato</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-6713e4ab19032d7afe606b30d2949f6817e2f379a7869f540bc26f44d03578473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amides - pharmacology</topic><topic>Amides - therapeutic use</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral resistance</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>Cytopathogenic Effect, Viral - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Resistance, Viral</topic><topic>Favipiravir</topic><topic>Humans</topic><topic>Influenza</topic><topic>Influenza A virus - drug effects</topic><topic>Influenza A virus - isolation & purification</topic><topic>Influenza, Human - drug therapy</topic><topic>Influenza, Human - virology</topic><topic>Microbial Sensitivity Tests</topic><topic>Neuraminidase - antagonists & inhibitors</topic><topic>Orthomyxoviridae - drug effects</topic><topic>Orthomyxoviridae - isolation & purification</topic><topic>Polymerase inhibitor</topic><topic>Pyrazines - pharmacology</topic><topic>Pyrazines - therapeutic use</topic><topic>T-705</topic><topic>Viral Proteins - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takashita, Emi</creatorcontrib><creatorcontrib>Ejima, Miho</creatorcontrib><creatorcontrib>Ogawa, Rie</creatorcontrib><creatorcontrib>Fujisaki, Seiichiro</creatorcontrib><creatorcontrib>Neumann, Gabriele</creatorcontrib><creatorcontrib>Furuta, Yousuke</creatorcontrib><creatorcontrib>Kawaoka, Yoshihiro</creatorcontrib><creatorcontrib>Tashiro, Masato</creatorcontrib><creatorcontrib>Odagiri, Takato</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takashita, Emi</au><au>Ejima, Miho</au><au>Ogawa, Rie</au><au>Fujisaki, Seiichiro</au><au>Neumann, Gabriele</au><au>Furuta, Yousuke</au><au>Kawaoka, Yoshihiro</au><au>Tashiro, Masato</au><au>Odagiri, Takato</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>2016-08</date><risdate>2016</risdate><volume>132</volume><spage>170</spage><epage>177</epage><pages>170-177</pages><issn>0166-3542</issn><eissn>1872-9096</eissn><abstract>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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27321665</pmid><doi>10.1016/j.antiviral.2016.06.007</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-9064-4699</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0166-3542 |
ispartof | Antiviral research, 2016-08, Vol.132, p.170-177 |
issn | 0166-3542 1872-9096 |
language | eng |
recordid | cdi_proquest_miscellaneous_1815701040 |
source | Elsevier ScienceDirect Journals Complete - AutoHoldings; MEDLINE |
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 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T09%3A50%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Antiviral%20susceptibility%20of%20influenza%20viruses%20isolated%20from%20patients%20pre-%20and%20post-administration%20of%20favipiravir&rft.jtitle=Antiviral%20research&rft.au=Takashita,%20Emi&rft.date=2016-08&rft.volume=132&rft.spage=170&rft.epage=177&rft.pages=170-177&rft.issn=0166-3542&rft.eissn=1872-9096&rft_id=info:doi/10.1016/j.antiviral.2016.06.007&rft_dat=%3Cproquest_cross%3E1810559790%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1810559790&rft_id=info:pmid/27321665&rft_els_id=S0166354216303382&rfr_iscdi=true |