{"created":"2024-06-10T01:36:29.120950+00:00","id":2000361,"links":{},"metadata":{"_buckets":{"deposit":"5e6e73ef-9935-4573-8e26-2a15186ec38e"},"_deposit":{"created_by":29,"id":"2000361","owners":[29],"pid":{"revision_id":0,"type":"depid","value":"2000361"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:02000361","sets":["57:86"]},"author_link":["144140"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2024-05-10","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2024-05-20"}]},"item_5_degree_grantor_53":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"鹿児島大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_42":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Philosophy in Medical Science","subitem_degreename_language":"en"}]},"item_5_description_17":{"attribute_name":"ファイル（説明）","attribute_value_mlt":[{"subitem_description":"博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"Influenza A virus (IAV) infection causes respiratory disease. Recently, infection of IAV H5N1 among mammals are reported in farmed mink. Therefore, to discover antivirals against IAV, we screened a compound library by using the RNA-dependent RNA polymerase (RdRp) assay system derived from H5N1 IAV including a drug-resistant PA mutant (I38T) and a viral polymerase activity enhancing PB2 mutant (T271A). Upon screening, we found vidofludimus can be served as a potential inhibitor for IAV. Vidofludimus an orally active inhibitor for dihydroorotate dehydrogenase (DHODH), a key enzyme for the cellular de novo pyrimidine biosynthesis pathway. We found that vidofludimus exerted antiviral activity against wild-type and drug-resistant mutant IAV, with effective concentrations (EC50) of 2.10 and 2.11 μM, respectively. The anti-IAV activity of vidofludimus was canceled by the treatment of uridine or cytidine through pyrimidine salvage synthesis pathway, or orotic acid through pyrimidine de novo synthesis pathway. This indicated that the main target of vidofludimus is DHODH in IAV RdRp expressing cells. We also produced recombinant seasonal IAV H1N1 virion and influenza B virus (IBV) RdRp assay system and confirmed vidofludimus also carried highly antiviral activity against seasonal IAV and IBV. Vidofludimus is a candidate drug for the future threat of IAV H5N1 infection among humans as well as seasonal influenza virus infection.","subitem_description_language":"en","subitem_description_type":"Other"},{"subitem_description":"Jiazhou Li, Midori Takeda, Mikiko Imahatakenaka, Masanori Ikeda\nIdentification of dihydroorotate dehydrogenase inhibitor, vidofludimus, as a potent and novel inhibitor for influenza virus\nJ Med Virol. 2024;96:e29372.\nhttps://doi.org/10.1002/jmv.29372","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_dissertation_number_55":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲総研第745号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"Wiley","subitem_publisher_language":"en"},{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"}]},"item_5_text_44":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"【指導教員:池田正徳】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2024-04-03"}]},"item_5_version_type_14":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"李, 佳洲","creatorNameLang":"ja"},{"creatorName":"Li, Jiazhou","creatorNameLang":"en"}],"familyNames":[{"familyName":"李","familyNameLang":"ja"},{"familyName":"Li","familyNameLang":"en"}],"givenNames":[{"givenName":"佳洲","givenNameLang":"ja"},{"givenName":"Jiazhou","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"144140","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2025-09-12"}],"displaytype":"detail","fileDate":[{"fileDateType":"Collected","fileDateValue":"2024-05-10"}],"filename":"Diss_Li_Jiazhou_ISK745_2024.pdf","filesize":[{"value":"2.1 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resistance","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"favipiravir","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"H5N1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"highly pathogenic","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"influenza virus","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"RdRp","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"vidofludimus","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Identification of dihydroorotate dehydrogenase inhibitor, vidofludimus, as a potent and novel inhibitor for influenza virus","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Identification of dihydroorotate dehydrogenase inhibitor, vidofludimus, as a potent and novel inhibitor for influenza virus","subitem_title_language":"en"},{"subitem_title":"ジヒドロオロチン酸デヒドロゲナーゼ阻害剤vidofludimusをインフルエンザウイルスに対する強力かつ新規な阻害剤として同定した","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"29","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-06-10"},"publish_date":"2024-06-10","publish_status":"0","recid":"2000361","relation_version_is_last":true,"title":["Identification of dihydroorotate dehydrogenase inhibitor, vidofludimus, as a potent and novel inhibitor for influenza virus"],"weko_creator_id":"29","weko_shared_id":-1},"updated":"2025-09-12T05:19:18.115545+00:00"}