WEKO3
アイテム
{"_buckets": {"deposit": "e1caac8e-4cbe-426f-b92b-49cd67504ff0"}, "_deposit": {"created_by": 2, "id": "2279", "owners": [2], "pid": {"revision_id": 0, "type": "depid", "value": "2279"}, "status": "published"}, "_oai": {"id": "oai:nagasaki-u.repo.nii.ac.jp:00002279", "sets": ["11"]}, "author_link": ["10595", "10598", "10597", "10594", "10593", "10599", "10596"], "item_2_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2017-03-08", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "3", "bibliographicPageStart": "e0173582", "bibliographicVolumeNumber": "12", "bibliographic_titles": [{"bibliographic_title": "PLOS ONE"}]}]}, "item_2_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Influenza viruses have acquired resistance to approved neuraminidase-targeting drugs, increasing the need for new drug targets for the development of novel anti-influenza drugs. Nucleoprotein (NP) is an attractive target since it has an indispensable role in virus replication and its amino acid sequence is well conserved. In this study, we aimed to identify new inhibitors of the NP using a structure-based drug discovery algorithm, named Nagasaki University Docking Engine (NUDE), which has been established especially for the Destination for GPU Intensive Machine (DEGIMA) supercomputer. The hit compounds that showed high binding scores during in silico screening were subsequently evaluated for anti-influenza virus effects using a cell-based assay. A 4-hydroxyquinolinone compound, designated as NUD-1, was found to inhibit the replication of influenza virus in cultured cells. Analysis of binding between NUD-1 and NP using surface plasmon resonance assay and fragment molecular orbital calculations confirmed that NUD-1 binds to NP and could interfere with NP-NP interactions essential for virus replication. Time-of-addition experiments showed that the compound inhibited the mid-stage of infection, corresponding to assembly of the NP and other viral proteins. Moreover, NUD-1 was also effective against various types of influenza A viruses including a clinical isolate of A(H1N1)pdm09 influenza with a 50% inhibitory concentration range of 1.8-2.1 μM. Our data demonstrate that the combined use of NUDE system followed by the cell-based assay is useful to obtain lead compounds for the development of novel anti-influenza drugs.", "subitem_description_type": "Abstract"}]}, "item_2_description_63": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "PLOS ONE, 12(3), e0173582; 2017", "subitem_description_type": "Other"}]}, "item_2_publisher_33": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "Public Library of Science"}]}, "item_2_relation_12": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type": "isIdenticalTo", "subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1371/journal.pone.0173582", "subitem_relation_type_select": "DOI"}}]}, "item_2_rights_13": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "c 2017 Makau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited."}]}, "item_2_source_id_8": {"attribute_name": "EISSN", "attribute_value_mlt": [{"subitem_source_identifier": "19326203", "subitem_source_identifier_type": "ISSN"}]}, "item_2_version_type_16": {"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_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Makau, Juliann Nzembi"}], "nameIdentifiers": [{"nameIdentifier": "10593", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Watanabe, Ken"}], "nameIdentifiers": [{"nameIdentifier": "10594", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ishikawa, Takeshi"}], "nameIdentifiers": [{"nameIdentifier": "10595", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Mizuta, Satoshi"}], "nameIdentifiers": [{"nameIdentifier": "10596", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hamada, Tsuyoshi"}], "nameIdentifiers": [{"nameIdentifier": "10597", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kobayashi, Nobuyuki"}], "nameIdentifiers": [{"nameIdentifier": "10598", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nishida, Noriyuki"}], "nameIdentifiers": [{"nameIdentifier": "10599", "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": "2020-12-21"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "PLoS12_173582.pdf", "filesize": [{"value": "2.6 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 2600000.0, "url": {"label": "PLoS12_173582.pdf", "url": "https://nagasaki-u.repo.nii.ac.jp/record/2279/files/PLoS12_173582.pdf"}, "version_id": "5448e041-9821-49df-8cd6-93b24c60cacd"}]}, "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": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches"}]}, "item_type_id": "2", "owner": "2", "path": ["11"], "permalink_uri": "http://hdl.handle.net/10069/37480", "pubdate": {"attribute_name": "公開日", "attribute_value": "2017-06-02"}, "publish_date": "2017-06-02", "publish_status": "0", "recid": "2279", "relation": {}, "relation_version_is_last": true, "title": ["Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches"], "weko_shared_id": -1}
Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches
http://hdl.handle.net/10069/37480
http://hdl.handle.net/10069/374806a152d04-4837-442b-a573-b22841609c5a
名前 / ファイル | ライセンス | アクション |
---|---|---|
PLoS12_173582.pdf (2.6 MB)
|
|
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2017-06-02 | |||||
タイトル | ||||||
タイトル | Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Makau, Juliann Nzembi
× Makau, Juliann Nzembi× Watanabe, Ken× Ishikawa, Takeshi× Mizuta, Satoshi× Hamada, Tsuyoshi× Kobayashi, Nobuyuki× Nishida, Noriyuki |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Influenza viruses have acquired resistance to approved neuraminidase-targeting drugs, increasing the need for new drug targets for the development of novel anti-influenza drugs. Nucleoprotein (NP) is an attractive target since it has an indispensable role in virus replication and its amino acid sequence is well conserved. In this study, we aimed to identify new inhibitors of the NP using a structure-based drug discovery algorithm, named Nagasaki University Docking Engine (NUDE), which has been established especially for the Destination for GPU Intensive Machine (DEGIMA) supercomputer. The hit compounds that showed high binding scores during in silico screening were subsequently evaluated for anti-influenza virus effects using a cell-based assay. A 4-hydroxyquinolinone compound, designated as NUD-1, was found to inhibit the replication of influenza virus in cultured cells. Analysis of binding between NUD-1 and NP using surface plasmon resonance assay and fragment molecular orbital calculations confirmed that NUD-1 binds to NP and could interfere with NP-NP interactions essential for virus replication. Time-of-addition experiments showed that the compound inhibited the mid-stage of infection, corresponding to assembly of the NP and other viral proteins. Moreover, NUD-1 was also effective against various types of influenza A viruses including a clinical isolate of A(H1N1)pdm09 influenza with a 50% inhibitory concentration range of 1.8-2.1 μM. Our data demonstrate that the combined use of NUDE system followed by the cell-based assay is useful to obtain lead compounds for the development of novel anti-influenza drugs. | |||||
書誌情報 |
PLOS ONE 巻 12, 号 3, p. e0173582, 発行日 2017-03-08 |
|||||
出版者 | ||||||
出版者 | Public Library of Science | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 19326203 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pone.0173582 | |||||
権利 | ||||||
権利情報 | c 2017 Makau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | PLOS ONE, 12(3), e0173582; 2017 |