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著作: [木戸 博]/[奥村 裕司]/[山田 博司]/Trong Q. Le/[矢野 仁康]/Proteases Essential for Human Influenza Virus Entry into Cells and Their Inhibitors as Potential Therapeutic Agents/[Current Pharmaceutical Design]

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EID
154926
EOID
690182
Map
0
LastModified
2013年6月10日(月) 14:04:19
Operator
松井 栄里
Avail
TRUE
Censor
0
Owner
木戸 博
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
  1. 徳島大学.分子酵素学研究センター(〜2007年3月31日/->組織[徳島大学.疾患酵素学研究センター])
著者 必須
  1. 木戸 博([徳島大学.先端酵素学研究所.重点研究部門])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 奥村 裕司
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. 山田 博司
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Trong Q. Le
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. 矢野 仁康
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Proteases Essential for Human Influenza Virus Entry into Cells and Their Inhibitors as Potential Therapeutic Agents

副題 任意
要約 任意

(英) Influenza A virus (IAV) is one of the most common infectious pathogens in humans. Since IVA genome does not have the processing protease for the viral membrane fusion glycoprotein precursors, entry of this virus into cells is determined primarily by host cellular, trypsin-type, processing proteases that proteolytically activate the fusion glycoprotein precursors of IAV. At least five different processing proteases have been identified in the airways of animals and humans. These proteases determine the infectious organ tropism of IAV infection as well as the efficiency of viral multiplication in the airway, and sometimes in the brain. Proteases in the upper respiratory tract are suppressed by secretory leukoprotease inhibitor, and those in the lower respiratory tract are suppressed by pulmonary surfactant which, by adsorption, inhibits the interaction between the proteases and viral membrane proteins. Since protease activities predominate over those of endogenous inhibitory compounds under normal airway conditions, administration of protease inhibitors in the early-stage of infection significantly suppresses viral entry and viral multiplication. Several viral neuraminidase inhibitors are used clinically as anti-influenza virus agents, based on their inhibitory action on viral release from infected cells. Furthermore, protease inhibitors of viral entry could be potentially useful against influenza virus as well as neuraminidase inhibitor-resistant viruses. We also found that ambroxol, a mucolytic and anti-oxidant agent, up-regulates the levels of endogenous protease inhibitory compounds in the airway fluids in early-phase infection, and that clarithromycin, a macrolide antibiotic, increases IgA levels and mucosal immunity through augmentation of interleukin-12 levels in the airway. The combination of neuraminidase inhibitors and protease inhibitors, clarithromycin or ambroxol, could be potentially used as a potent anti-influenza therapy to minimize the emergence of drug-resistant mutant viruses.

キーワード 推奨
  1. (英) Ambroxol
  2. (英) Animals
  3. (英) Antiviral Agents
  4. (英) Brain
  5. (英) Clarithromycin
  6. (英) Drug Therapy, Combination
  7. (英) Expectorants
  8. (英) Hemagglutinin Glycoproteins, Influenza Virus
  9. (英) Humans
  10. (英) Influenza A virus
  11. (英) Influenza, Human
  12. (英) Neuraminidase
  13. (英) Peptide Hydrolases
  14. (英) Protease Inhibitors
  15. (英) Protein Processing, Post-Translational
  16. (英) Pulmonary Surfactants
  17. (英) Respiratory System
  18. (英) Secretory Leukocyte Peptidase Inhibitor
  19. (英) Virus Replication
発行所 推奨
誌名 必須 Current Pharmaceutical Design(Bentham Science Publishers)
(pISSN: 1381-6128, eISSN: 1873-4286)
ISSN 任意 1873-4286
ISSN: 1381-6128 (pISSN: 1381-6128, eISSN: 1873-4286)
Title: Current pharmaceutical design
Title(ISO): Curr Pharm Des
Publisher: Bentham Science Publishers
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 13
必須 4
必須 405 414
都市 任意
年月日 必須 2007年 4月 1日
URL 任意
DOI 任意 10.2174/138161207780162971    (→Scopusで検索)
PMID 任意 17311557    (→Scopusで検索)
NAID 任意
WOS 任意 000245200900005
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan. kido@ier.tokushima-u.ac.jp

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't

  4. (英) Article.PublicationTypeList.PublicationType: Review

  5. (英) NumberOfReferences: 58