Studies on the molecular mechanism of cell-entry inhibitors for hand-foot-and-mouth disease virus.

• Project/Area Number: 15K08512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Nishimura Yorihiro 国立感染症研究所, ウイルス第二部, 主任研究官 (00392316)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 手足口病 / エンテロウイルス71 / 受容体 / PSGL-1 / ヘパラン硫酸 / 感染阻害剤 / 化合物 / 感染阻害 / 低分子化合物 / 阻害剤 / NF449 / 阻害 / SCARB2

Outline of Final Research Achievements

Enterovirus 71 (EV71) is one of the pathogens of hand, foot, and mouth disease and various neurological symptoms including fatal encephalitis in young children. There are no specific therapies available. In this study, I focused on the anti-EV71 compound, NF449. I clarified how NF449 inhibits EV71 replication in vitro. I found that NF449 interacts with the EV71 capsid and prevents virus attachment to the receptor molecules on the cell surface. This work provides information that may facilitate development of improved antiviral compounds that block the attachment of EV71 to cellular receptors.

Research Products

• [Int'l Joint Research] The Children’s Hospital of Philadelphia/University of Pennsylvania/Pennsylvania State University(米国)
• [Journal Article] The suramin derivative NF449 interacts with the 5-fold vertex of the enterovirus A71 capsid to prevent virus attachment to PSGL-1 and heparan sulfate (2015)
  • Author(s): Nishimura Y, McLaughlin NP, Pan J, Goldstein S, Hafenstein S, Shimizu H, Winkler JD, Bergelson JM
  • Journal Title: PLoS Pathogens Volume: 11 Issue: 10 Pages: e1005184-e1005184
  • DOI: 10.1371/journal.ppat.1005184
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] エンテロウイルス71と受容体PSGL-1の結合とその制御 (2017)
  • Author(s): 西村順裕
  • Organizer: 東京大学医科学研究所 平成28年度若手研究者シンポジウム 「若手研究者が切り拓く次世代ウイルス学」
  • Place of Presentation: 東京都港区
  • Year and Date: 2017-02-17
  • Invited
• [Presentation] The suramin derivative NF449 interacts with the 5-fold vertex of the EV71 capsid to prevent virus attachment to PSGL-1 and heparan sulfate (2015)
  • Author(s): Nishimura Y, McLaughlin N, Pan J, Goldstein S, Hafenstein S, Shimizu H, Winkler JD, Bergelson JM
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2015-11-22
• [Presentation] The suramin derivative NF449 interacts with the 5-fold vertex of the EV71 capsid to prevent virus attachment to PSGL-1 and heparan sulfate (2015)
  • Author(s): Nishimura Y, McLaughlin N, Pan J, Goldstein S, Hafenstein S, Shimizu H, Winkler JD, Bergelson JM
  • Organizer: 10th Asia-Pacific Congress of Medical Virology 2015
  • Place of Presentation: 台北、台湾
  • Year and Date: 2015-10-15
  • Int'l Joint Research / Invited