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New Indications for HSP90 and HSP70 Inhibitors as Antiviral Drugs

  • Chapter
Book cover Heat Shock Protein-Based Therapies

Part of the book series: Heat Shock Proteins ((HESP,volume 9))

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Abstract

Viruses infect host cells and elicit a broad range of ailments. The viral genome is relatively small and therefore viruses are reliant on host factors throughout the viral lifecycle. The molecular chaperones, heat shock proteins 70 (HSP70) and 90 (HSP90), have been shown to be host factors that are utilized by a wide range of viruses, including HIV, influenza, polioviurs, and dengue virus for replication and propagation. There is an observed increase in HSP70 and HSP90 expression following viral infection. Additionally, HSP70 and HSP90 regulate anti-apoptotic pathways and assist in the proper folding of newly synthesized proteins during the viral lifecycle. The utilization of HSP70 and HSP90 in viral propagation is similar to the roles of these proteins in cancer progression. Small molecule inhibitors have been developed for both HSP70 and HSP90 as anticancer therapeutics, but there is recent evidence to suggest these inhibitors have indications as antiviral drugs. This chapter aims to highlight the roles of HSP70 and HSP90 in the lifecycle of numerous viruses. Furthermore, this will highlight the potential for already developed HSP70 and HSP90 inhibitors as antivirals and the development of further antiviral drugs targeting these proteins.

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Abbreviations

17-AAG:

17-N-allylamino-17-demethoxygeldanamycin

17-DMAG:

1 7-Dimethylaminoethylamino-17-demethoxygeldanamycin

Aha1:

Activator of heat shock 90 kDa protein ATPase homolog 1

Apaf-1:

Apoptotic protease-activating factor-1

Azt:

Azidothymidine

Bax:

Bcl2-associated X protein

Bcl-2:

B-cell lymphoma-2

Cdc37:

Cell division cycle 37

Cdk9:

Cyclin-dependent kinase 9

CHIP:

Carboxyl-terminus of HSP70 interacting protein

Cyp40:

Cyclophilin 40

E1A:

Early region 1A

FLIP(S):

FLICE inhibitory protein

GRP75//78/94:

Glucose regulated protein 75/78/94

Hip:

HSP70-interacting protein

Hop:

HSP70-HSP90 organizing protein

JNK:

c-Jun N-terminal kinase

pRB:

Retinoblastoma protein

TPR:

Tetratricopeptide repeat

VP1/2/3/4/7:

Viral protein 1/2/3/4/7

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Acknowledgements

This work was funded by grants R01-AI089526-04 and a Department of Defense Transformative Vision Award to T.A.J.H.

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Authors and Affiliations

  1. Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, 27710, USA

    Matthew K. Howe & Timothy A. J. Haystead

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  1. Matthew K. Howe
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  2. Timothy A. J. Haystead
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Correspondence to Timothy A. J. Haystead .

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Editors and Affiliations

  1. Professor and VD for Research Innovations, Deanship for Scientific Research,, University of Dammam, Dammam, Saudi Arabia

    Alexzander A.A. Asea

  2. Deanship for Scientific Research and Preventive Dental Sciences Department, College of Dentistry, University of Dammam, Dammam, Saudi Arabia

    Naif N. Almasoud

  3. Gastrointestinal Translational Research, Center for Radiation Oncology Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Sunil Krishnan

  4. Department of Microbiology, Immunology & Biochemistry, Morehouse School of Medicine, Atlanta, Georgia, USA

    Punit Kaur

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Howe, M.K., Haystead, T.A.J. (2015). New Indications for HSP90 and HSP70 Inhibitors as Antiviral Drugs. In: Asea, A., Almasoud, N., Krishnan, S., Kaur, P. (eds) Heat Shock Protein-Based Therapies. Heat Shock Proteins, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-17211-8_10

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