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Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.
Biochem J. 2012 May 01; 443(3):851-6.BJ

Abstract

The movement of proteins between the cytoplasm and nucleus mediated by the importin superfamily of proteins is essential to many cellular processes, including differentiation and development, and is critical to disease states such as viral disease and oncogenesis. We recently developed a high-throughput screen to identify specific and general inhibitors of protein nuclear import, from which ivermectin was identified as a potential inhibitor of importin α/β-mediated transport. In the present study, we characterized in detail the nuclear transport inhibitory properties of ivermectin, demonstrating that it is a broad-spectrum inhibitor of importin α/β nuclear import, with no effect on a range of other nuclear import pathways, including that mediated by importin β1 alone. Importantly, we establish for the first time that ivermectin has potent antiviral activity towards both HIV-1 and dengue virus, both of which are strongly reliant on importin α/β nuclear import, with respect to the HIV-1 integrase and NS5 (non-structural protein 5) polymerase proteins respectively. Ivermectin would appear to be an invaluable tool for the study of protein nuclear import, as well as the basis for future development of antiviral agents.

Authors+Show Affiliations

Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22417684

Citation

Wagstaff, Kylie M., et al. "Ivermectin Is a Specific Inhibitor of Importin Α/β-mediated Nuclear Import Able to Inhibit Replication of HIV-1 and Dengue Virus." The Biochemical Journal, vol. 443, no. 3, 2012, pp. 851-6.
Wagstaff KM, Sivakumaran H, Heaton SM, et al. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851-6.
Wagstaff, K. M., Sivakumaran, H., Heaton, S. M., Harrich, D., & Jans, D. A. (2012). Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. The Biochemical Journal, 443(3), 851-6. https://doi.org/10.1042/BJ20120150
Wagstaff KM, et al. Ivermectin Is a Specific Inhibitor of Importin Α/β-mediated Nuclear Import Able to Inhibit Replication of HIV-1 and Dengue Virus. Biochem J. 2012 May 1;443(3):851-6. PubMed PMID: 22417684.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. AU - Wagstaff,Kylie M, AU - Sivakumaran,Haran, AU - Heaton,Steven M, AU - Harrich,David, AU - Jans,David A, PY - 2012/3/16/entrez PY - 2012/3/16/pubmed PY - 2012/6/9/medline SP - 851 EP - 6 JF - The Biochemical journal JO - Biochem J VL - 443 IS - 3 N2 - The movement of proteins between the cytoplasm and nucleus mediated by the importin superfamily of proteins is essential to many cellular processes, including differentiation and development, and is critical to disease states such as viral disease and oncogenesis. We recently developed a high-throughput screen to identify specific and general inhibitors of protein nuclear import, from which ivermectin was identified as a potential inhibitor of importin α/β-mediated transport. In the present study, we characterized in detail the nuclear transport inhibitory properties of ivermectin, demonstrating that it is a broad-spectrum inhibitor of importin α/β nuclear import, with no effect on a range of other nuclear import pathways, including that mediated by importin β1 alone. Importantly, we establish for the first time that ivermectin has potent antiviral activity towards both HIV-1 and dengue virus, both of which are strongly reliant on importin α/β nuclear import, with respect to the HIV-1 integrase and NS5 (non-structural protein 5) polymerase proteins respectively. Ivermectin would appear to be an invaluable tool for the study of protein nuclear import, as well as the basis for future development of antiviral agents. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/22417684/full_citation L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20120150 DB - PRIME DP - Unbound Medicine ER -