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[{"key": "dc.contributor.advisor", "value": "Marjom\u00e4ki, Varpu", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Laajala, Mira", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Kalander, Kerttu", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2021-05-17T06:22:00Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2021-05-17T06:22:00Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2021", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/75666", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Enterovirusten sukuun sis\u00e4ltyy suuri m\u00e4\u00e4r\u00e4 viruslajeja, jotka aiheuttavat tyypillisesti lievi\u00e4 flunssan oireita, mutta niiden tiedet\u00e4\u00e4n my\u00f6s johtavan vakavampiin akuutteihin ja kroonisiin tulehduksiin. Ne on my\u00f6s yhdistetty tyypin 1 diabetekseen, syd\u00e4nkohtauksiin ja aivohalvaukseen sek\u00e4 aiheuttavat enterorokko-epidemioita. Toistaiseksi enteroviruksia vastaan ei kuitenkaan ole saatavilla virusl\u00e4\u00e4kkeit\u00e4, mink\u00e4 vuoksi ne ovatkin t\u00e4rke\u00e4 l\u00e4\u00e4kkeiden ja rokotteiden kehityskohde. T\u00e4ss\u00e4 tutkimuksessa 201 synteettist\u00e4 molekyyli\u00e4 seulottiin mahdollisen antiviraaliefektin selvitt\u00e4miseksi ja n\u00e4in valikoitujen yksil\u00f6iden inhibiitiokyky\u00e4 ja mekanismia analysoitiin pidemm\u00e4lle. Seulonnat suoritettiin infektoimalla soluja Coxsackievirus A9:ll\u00e4 ja Coxsackievirus B3:lla molekyylien l\u00e4sn\u00e4ollessa, mink\u00e4 j\u00e4lkeen infektion inhibitiota arvioitiin kristalliviolettiv\u00e4rj\u00e4yksell\u00e4 ja absorbanssimittauksilla. Konsentraatiosarjojen avulla tutkitut molekyylit rajattiin kolmeen kaikkein potentiaalisimpaan, joista kaksi oli erityisen kiinnostavia niiden inhibitiokyvyn ja alhaisen toksisuuden ansiosta. Jotta pystyttiin muodostamaan kuva molekyylien inhibiitiomekanismista, tehtiin useita kokeita, jotka keskittyiv\u00e4t erityisesti viruskapsidiin kohdistuvien vaikutusten selvitt\u00e4miseen. Kokeisiin kuului \u2019time-of-addition\u2019, \u2018uncoating\u2019 ja radioaktiivinen gradienttikoe ja lis\u00e4ksi molekyyleill\u00e4 k\u00e4siteltyj\u00e4 viruksia kuvannettiin elektronimikroskoopilla. Tulokset viittaavat siihen, ett\u00e4 molekyylik\u00e4sittelyn j\u00e4lkeen viruskapsidi s\u00e4ilyy ehj\u00e4n\u00e4, viruksen kapsidin avautuminen v\u00e4henee ja optimaalisen inhibition saamiseksi riitt\u00e4\u00e4, ett\u00e4 molekyyli on l\u00e4sn\u00e4 ennen viruksen lis\u00e4\u00e4mist\u00e4 soluille. N\u00e4iden perusteella on todenn\u00e4k\u00f6ist\u00e4, ett\u00e4 n\u00e4m\u00e4 kolme molekyyli\u00e4 sitoutuvat viruskapsidiin, stabiloivat sit\u00e4 ja sen my\u00f6t\u00e4 est\u00e4v\u00e4t virusgenomin vapautumisen. L\u00f6ydetyt molekyylit ovat mielenkiintoisia kohteita lis\u00e4tutkimuksille muun muassa niiden rakenteen ja mahdollisten sitoutumiskohtien yhteyden selvitt\u00e4misen saralla. Tulevaisuudessa my\u00f6s toimivuus muita enterovirusserotyyppej\u00e4 vastaan on mielek\u00e4st\u00e4 tutkia. Kaiken kaikkiaan erityisesti kaksi molekyyleist\u00e4 ovat hyvi\u00e4 kohteita jatkotutkimuksille ja mahdolliselle antiviraalil\u00e4\u00e4kekehitykselle. Molekyylit antavat my\u00f6s arvokasta tietoa, jota voidaan k\u00e4ytt\u00e4\u00e4 uusien synteettisten molekyylien suunnitteluun.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "The enterovirus genus consists of a number of virus species which are known to cause diseases that range from mild flu to more serious acute and chronic inflammations, yet they lack available antivirals. The viruses are also associated with type 1 diabetes, heart attack and acute stroke and have been the cause of hand, foot and mouth epidemics which makes enteroviruses a very just target for antiviral as well as vaccine development. In this study, 201 synthetic molecules were screened for antiviral activity and those showing potential were further studied to examine their inhibition mechanism and efficacy. Initial screenings were performed by infecting cells with Coxsackievirus A9 and Coxsackievirus B3 in the presence of the synthetic molecules after which inhibition was analysed with crystal violet staining and absorbance measurements. The molecules were narrowed down to the three most potential ones with concentration series, two of them being particularly interesting due to good inhibition and low cytotoxicity. An idea of the possible inhibition mechanism was formed with a combination of time-of-addition assays, radioactive gradient assay, uncoating assay and imaging of the viruses with transmission electron microscopy. Results indicated that the virus capsid remains intact after molecule treatments, the molecules reduce viral uncoating and, to get effective inhibition, the presence prior to adding the virus onto cells is enough. Thus, it was concluded that two of the discovered potential antivirals likely bind to the virus capsid, stabilize it and, in doing so, prevent the virus from releasing its genome. The molecules are attractive for further research of the molecule structures, analysis of potential binding sites and possible tests with other enterovirus serotypes to asses broad spectrum effectiveness. These molecules could be considered for antiviral drug development or at the least give valuable information which can be used to design new synthetic molecules with even more effective structures.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2021-05-17T06:22:00Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2021-05-17T06:22:00Z (GMT). No. of bitstreams: 0\n Previous issue date: 2021", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "43", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "antivirals", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "synthetic molecules", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Coxsackievirus A9", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Coxsackievirus B3", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Antiviral study of synthetic molecules on enteroviruses", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202105172940", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "seulonta", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "enterovirukset", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "inhibiittorit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "kapsidi", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "screening analysis", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "enteroviruses", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "inhibitors", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "capsid", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "The author has not given permission to make the work publicly available electronically. Therefore the material can be read only at the archival workstation at Jyv\u00e4skyl\u00e4 University Library (https://kirjasto.jyu.fi/collections/archival-workstation).", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Tekij\u00e4 ei ole antanut lupaa avoimeen julkaisuun, joten aineisto on luettavissa vain Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6semalta. Ks. https://kirjasto.jyu.fi/kokoelmat/arkistotyoasema..", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
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