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dc.contributor.authorSmielewska, Anna Alexandraen
dc.contributor.authorEmmott, Edwarden
dc.contributor.authorGoodfellow, Ianen
dc.contributor.authorJalal, Hamiden
dc.date.accessioned2018-05-03T13:35:17Z
dc.date.available2018-05-03T13:35:17Z
dc.date.issued2018-05en
dc.identifier.issn1386-6532
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/275515
dc.description.abstractABSTRACT Background Human parainfluenza type 3 (HPIV3) is an important respiratory pathogen. Although a number of potential therapeutic candidates exist, there is currently no licensed therapy or vaccine. Ribavirin (RBV), favipiravir (FVP) and zanamivir (ZNV) are inhibitors with proven activity against influenza and with potential inhibitory activity against HPIV3 laboratory adapted strains in vitro. Objectives To evaluate RBV, FVP and ZNV as inhibitors of minimally passaged UK clinical strains of HPIV3 as well as a laboratory adapted strain MK9 in vitro. Study Design The inhibitory action of RBV, FVP and ZNV was evaluated against nine minimally passaged clinical strains and a laboratory adapted strain MK9 using plaque reduction and growth curve inhibition in a cell culture model. Results Clinical isolates were found to be at least as susceptible as the laboratory adapted strains to RBV and FVP and significantly more susceptible to ZNV. However the inhibitory concentrations achieved by ZNV against clinical strains remain prohibitively high in vivo. Conclusions: RBV, FVP and ZNV were found to be effective inhibitors of HPIV3 in vitro. The lack of efficacy of RBV in vivo may be due to inability to reach required therapeutic levels. FVP, on the other hand, is a good potential therapeutic agent against HPIV3. Further studies using wild type clinical strains, as well as better formulation and delivery mechanisms may improve the utility of these three inhibitors.
dc.description.sponsorshipThis work was supported by Public Health England (PHE) PhD studentship fund 2013
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.subjectCell Line, Tumoren
dc.subjectHumansen
dc.subjectParainfluenza Virus 3, Humanen
dc.subjectRespirovirus Infectionsen
dc.subjectAmidesen
dc.subjectPyrazinesen
dc.subjectRibavirinen
dc.subjectAntiviral Agentsen
dc.subjectCytopathogenic Effect, Viralen
dc.subjectVirus Replicationen
dc.subjectZanamiviren
dc.subjectVirus Attachmenten
dc.titleIn vitro sensitivity of human parainfluenza 3 clinical isolates to ribavirin, favipiravir and zanamivir.en
dc.typeArticle
prism.endingPage26
prism.publicationDate2018en
prism.publicationNameJournal of clinical virology : the official publication of the Pan American Society for Clinical Virologyen
prism.startingPage19
prism.volume102en
dc.identifier.doi10.17863/CAM.22751
dcterms.dateAccepted2018-02-13en
rioxxterms.versionofrecord10.1016/j.jcv.2018.02.009en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2018-05en
dc.contributor.orcidSmielewska, Anna [0000-0002-6200-6876]
dc.contributor.orcidGoodfellow, Ian [0000-0002-9483-510X]
dc.identifier.eissn1873-5967
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (097997/Z/11/Z)
pubs.funder-project-idPublic Health England (PHE) (PHE PhD Studentship Fund 2013)
rioxxterms.freetoread.startdate2019-02-15


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