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Small molecule inhibitors reveal Niemann–Pick C1 is essential for Ebola virus infection

Author

Listed:
  • Marceline Côté

    (Brigham and Women’s Hospital)

  • John Misasi

    (Brigham and Women’s Hospital
    Children’s Hospital)

  • Tao Ren

    (New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, Harvard Medical School)

  • Anna Bruchez

    (Brigham and Women’s Hospital)

  • Kyungae Lee

    (New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, Harvard Medical School)

  • Claire Marie Filone

    (Brigham and Women’s Hospital
    United States Army Medical Research Institute of Infectious Diseases)

  • Lisa Hensley

    (United States Army Medical Research Institute of Infectious Diseases)

  • Qi Li

    (Brigham and Women’s Hospital)

  • Daniel Ory

    (Diabetic Cardiovascular Disease Center, Washington University School of Medicine)

  • Kartik Chandran

    (Brigham and Women’s Hospital
    Present address: Department of Microbiology and Immunobiology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.)

  • James Cunningham

    (Brigham and Women’s Hospital
    Harvard Medical School)

Abstract

Filovirus infectivity factors The extraordinary virulence of the Ebola and Marburg filoviruses has spurred intensive research into the molecular mechanisms by which they multiply and cause disease. Carette et al. use a genome-wide genetic screen in human cells to identify factors required for entry of Ebola virus. The screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann–Pick C1 (NPC1). Côté et al. report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection in cell culture, with NPC1 being the target. The unexpected role for the hereditary disease gene NPC1 in Ebola virus infection may facilitate the development of antifilovirus therapeutics.

Suggested Citation

  • Marceline Côté & John Misasi & Tao Ren & Anna Bruchez & Kyungae Lee & Claire Marie Filone & Lisa Hensley & Qi Li & Daniel Ory & Kartik Chandran & James Cunningham, 2011. "Small molecule inhibitors reveal Niemann–Pick C1 is essential for Ebola virus infection," Nature, Nature, vol. 477(7364), pages 344-348, September.
    • Handle: RePEc:nat:nature:v:477:y:2011:i:7364:d:10.1038_nature10380
    DOI: 10.1038/nature10380
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    Cited by:

    1. Massimo Florio & Simona Gamba, 2021. "Biomed Europa: After the coronavirus, a public infrastructure to overcome the pharmaceutical oligopoly," Annals of Public and Cooperative Economics, Wiley Blackwell, vol. 92(3), pages 387-409, September.
    2. Gamba, Simona & Magazzini, Laura & Pertile, Paolo, 2021. "R&D and market size: Who benefits from orphan drug legislation?," Journal of Health Economics, Elsevier, vol. 80(C).
    3. Vanessa Monteil & Hyesoo Kwon & Lijo John & Cristiano Salata & Gustav Jonsson & Sabine U. Vorrink & Sofia Appelberg & Sonia Youhanna & Matheus Dyczynski & Alexandra Leopoldi & Nicole Leeb & Jennifer V, 2023. "Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Ilyas Khan & Sunan Li & Lihong Tao & Chong Wang & Bowei Ye & Huiyu Li & Xiaoyang Liu & Iqbal Ahmad & Wenqiang Su & Gongxun Zhong & Zhiyuan Wen & Jinliang Wang & Rong-Hong Hua & Ao Ma & Jie Liang & Xia, 2024. "Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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