{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360021390744264064.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/s42003-023-04888-x"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s42003-023-04888-x.pdf"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s42003-023-04888-x"}},{"identifier":{"@type":"PMID","@value":"37173432"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>Remdesivir is an antiviral drug used for COVID-19 treatment worldwide. Cardiovascular side effects have been associated with remdesivir; however, the underlying molecular mechanism remains unknown. Here, we performed a large-scale G-protein-coupled receptor screening in combination with structural modeling and found that remdesivir is a selective, partial agonist for urotensin-II receptor (UTS2R) through the Gα<jats:sub>i/o</jats:sub>-dependent AKT/ERK axis. Functionally, remdesivir treatment induced prolonged field potential and APD<jats:sub>90</jats:sub> in human induced pluripotent stem cell (iPS)-derived cardiomyocytes and impaired contractility in both neonatal and adult cardiomyocytes, all of which mirror the clinical pathology. Importantly, remdesivir-mediated cardiac malfunctions were effectively attenuated by antagonizing UTS2R signaling. Finally, we characterized the effect of 110 single-nucleotide variants in <jats:italic>UTS2R</jats:italic> gene reported in genome database and found four missense variants that show gain-of-function effects in the receptor sensitivity to remdesivir. Collectively, our study illuminates a previously unknown mechanism underlying remdesivir-related cardiovascular events and that genetic variations of <jats:italic>UTS2R</jats:italic> gene can be a potential risk factor for cardiovascular events during remdesivir treatment, which collectively paves the way for a therapeutic opportunity to prevent such events in the future.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420564276170129664","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00868565"},{"@type":"NRID","@value":"1000000868565"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/00868565"}],"foaf:name":[{"@value":"Akiko Ogawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744263945","@type":"Researcher","foaf:name":[{"@value":"Seiya Ohira"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744263963","@type":"Researcher","foaf:name":[{"@value":"Yuri Kato"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744263983","@type":"Researcher","foaf:name":[{"@value":"Tatsuya Ikuta"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744263953","@type":"Researcher","foaf:name":[{"@value":"Shota Yanagida"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744264082","@type":"Researcher","foaf:name":[{"@value":"Xinya Mi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744263959","@type":"Researcher","foaf:name":[{"@value":"Yukina Ishii"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744263984","@type":"Researcher","foaf:name":[{"@value":"Yasunari Kanda"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326225943040","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"90342641"},{"@type":"NRID","@value":"1000090342641"},{"@type":"ORCID","@value":"0000-0002-2587-5458"},{"@type":"J_GLOBAL","@value":"200901054525564283"},{"@type":"NRID","@value":"9000018181956"},{"@type":"NRID","@value":"9000414836342"},{"@type":"NRID","@value":"9000413516828"},{"@type":"NRID","@value":"9000412112407"},{"@type":"NRID","@value":"9000301734767"},{"@type":"NRID","@value":"9000360556340"},{"@type":"NRID","@value":"9000283732808"},{"@type":"NRID","@value":"9000411831999"},{"@type":"NRID","@value":"9000241186294"},{"@type":"NRID","@value":"9000000712775"},{"@type":"NRID","@value":"9000018827528"},{"@type":"NRID","@value":"9000412603804"},{"@type":"NRID","@value":"9000356878967"},{"@type":"NRID","@value":"9000413511521"},{"@type":"NRID","@value":"9000412104599"},{"@type":"NRID","@value":"9000386309518"},{"@type":"NRID","@value":"9000019034353"},{"@type":"NRID","@value":"9000395378429"},{"@type":"NRID","@value":"9000356905319"},{"@type":"NRID","@value":"9000411831020"},{"@type":"NRID","@value":"9000021203090"},{"@type":"NRID","@value":"9000317154675"},{"@type":"NRID","@value":"9000415427470"},{"@type":"NRID","@value":"9000391399719"},{"@type":"NRID","@value":"9000414534123"},{"@type":"NRID","@value":"9000413477499"},{"@type":"NRID","@value":"9000411581167"},{"@type":"NRID","@value":"9000241868590"},{"@type":"NRID","@value":"9000297476983"},{"@type":"NRID","@value":"9000370257219"},{"@type":"NRID","@value":"9000345336241"},{"@type":"NRID","@value":"9000397801797"},{"@type":"NRID","@value":"9000001824720"},{"@type":"NRID","@value":"9000347362009"},{"@type":"NRID","@value":"9000347139029"},{"@type":"NRID","@value":"9000411832088"},{"@type":"NRID","@value":"9000411100857"},{"@type":"NRID","@value":"9000411100313"},{"@type":"NRID","@value":"9000273020351"},{"@type":"NRID","@value":"9000241873158"},{"@type":"NRID","@value":"9000403438801"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0057226"}],"foaf:name":[{"@value":"Motohiro Nishida"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801209622016","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"50525813"},{"@type":"NRID","@value":"1000050525813"},{"@type":"ORCID","@value":"0000-0003-0805-4049"},{"@type":"NRID","@value":"9000259342327"},{"@type":"NRID","@value":"9000006814912"},{"@type":"NRID","@value":"9000364748132"},{"@type":"NRID","@value":"9000409850137"},{"@type":"NRID","@value":"9000409849359"},{"@type":"NRID","@value":"9000412296704"},{"@type":"NRID","@value":"9000409849643"},{"@type":"NRID","@value":"9000314381372"},{"@type":"NRID","@value":"9000333086660"},{"@type":"NRID","@value":"9000364748002"},{"@type":"NRID","@value":"9000364748134"},{"@type":"NRID","@value":"9000414550553"},{"@type":"NRID","@value":"9000397946286"},{"@type":"NRID","@value":"9000364748139"},{"@type":"NRID","@value":"9000411105646"},{"@type":"NRID","@value":"9000409849004"},{"@type":"NRID","@value":"9000284276666"},{"@type":"NRID","@value":"9000409581175"},{"@type":"NRID","@value":"9000402125273"},{"@type":"NRID","@value":"9000409849894"},{"@type":"NRID","@value":"9000243723580"},{"@type":"NRID","@value":"9000402609167"},{"@type":"NRID","@value":"9000409849059"},{"@type":"NRID","@value":"9000409849134"},{"@type":"NRID","@value":"9000412400894"},{"@type":"NRID","@value":"9000381958831"},{"@type":"NRID","@value":"9000409849919"},{"@type":"NRID","@value":"9000409849415"},{"@type":"NRID","@value":"9000364748142"},{"@type":"NRID","@value":"9000398998174"},{"@type":"NRID","@value":"9000364748136"},{"@type":"NRID","@value":"9000403105337"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/iaska"}],"foaf:name":[{"@value":"Asuka Inoue"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390744263951","@type":"Researcher","foaf:name":[{"@value":"Fan-Yan Wei"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"23993642"}],"prism:publicationName":[{"@value":"Communications Biology"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2023-05-12","prism:volume":"6","prism:number":"1","prism:startingPage":"511"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0","https://creativecommons.org/licenses/by/4.0"],"url":[{"@id":"https://www.nature.com/articles/s42003-023-04888-x.pdf"},{"@id":"https://www.nature.com/articles/s42003-023-04888-x"}],"createdAt":"2023-05-12","modifiedAt":"2023-05-12","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Heart%20Failure","dc:title":"Heart Failure"},{"@id":"https://cir.nii.ac.jp/all?q=QH301-705.5","dc:title":"QH301-705.5"},{"@id":"https://cir.nii.ac.jp/all?q=Induced%20Pluripotent%20Stem%20Cells","dc:title":"Induced Pluripotent Stem Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Infant,%20Newborn","dc:title":"Infant, Newborn"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=COVID-19","dc:title":"COVID-19"},{"@id":"https://cir.nii.ac.jp/all?q=Myocytes,%20Cardiac","dc:title":"Myocytes, Cardiac"},{"@id":"https://cir.nii.ac.jp/all?q=Biology%20(General)","dc:title":"Biology (General)"},{"@id":"https://cir.nii.ac.jp/all?q=Antiviral%20Agents","dc:title":"Antiviral Agents"},{"@id":"https://cir.nii.ac.jp/all?q=Article","dc:title":"Article"},{"@id":"https://cir.nii.ac.jp/all?q=COVID-19%20Drug%20Treatment","dc:title":"COVID-19 Drug Treatment"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20G-Protein-Coupled","dc:title":"Receptors, 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therapeutics"}]},{"@id":"https://cir.nii.ac.jp/crid/1040289864808971136","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"21H05113"},{"@type":"JGN","@value":"JP21H05113"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PLANNED-21H05113/"}],"notation":[{"@language":"ja","@value":"オピオイド受容体の網羅的シグナル解析による薬理経路の同定"},{"@language":"en","@value":"Identification of pharmacologically relevant signaling pathways at opioid receptors"}]},{"@id":"https://cir.nii.ac.jp/crid/1040291932574339072","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22H04628"},{"@type":"JGN","@value":"JP22H04628"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PUBLICLY-22H04628/"}],"notation":[{"@language":"ja","@value":"新規修飾RNAメタボライトによるオートファジー経路の解明"},{"@language":"en","@value":"Investigation of the mechanism of autophagy pathway by novel metabolites derived from modified 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