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  • Review Article
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Therapeutic strategies to target the Ebola virus life cycle

Nature Reviews Microbiology volume 17, pages 593–606 (2019)Cite this article

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Abstract

Following the Ebola virus disease epidemic in west Africa, there has been increased awareness of the need for improved therapies for emerging diseases, including viral haemorrhagic fevers such as those caused by Ebola virus and other filoviruses. Our continually improving understanding of the virus life cycle coupled with the increased availability of ‘omics’ analyses and high-throughput screening technologies has enhanced our ability to identify potential viral and host factors and aspects involved in the infection process that might be intervention targets. In this Review we address compounds that have shown promise to various degrees in interfering with the filovirus life cycle, including monoclonal antibodies such as ZMapp, mAb114 and REGN-EB3 and inhibitors of viral RNA synthesis such as remdesivir and TKM-Ebola. Furthermore, we discuss the general potential of targeting aspects of the virus life cycle such as the entry process, viral RNA synthesis and gene expression, as well as morphogenesis and budding.

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Fig. 1: Ebola virus genome structure and life cycle.
Fig. 2: Inhibitors of the viral entry process.
Fig. 3: Targeting viral RNA transcription and replication.
Fig. 4: Theoretical targets in the morphogenesis and budding process.

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Acknowledgements

Work in the authors’ laboratories was funded in part by the Friedrich-Loeffler-Institut and in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

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  1. These authors contributed equally: Thomas Hoenen, Allison Groseth

Authors and Affiliations

  1. Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Insel Riems, Greifswald, Germany

    Thomas Hoenen

  2. Junior Research Group Arenavirus Biology, Friedrich-Loeffler-Institut, Insel Riems, Greifswald, Germany

    Allison Groseth

  3. Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA

    Heinz Feldmann

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T.H., A.G. and H.F. researched data for the article, contributed substantially to the discussion of content, wrote the article and reviewed and edited the manuscript before submission.

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Glossary

Haemorrhagic fever

A disease that is characterized by fever and in severe cases associated with bleeding manifestations as a result of dysregulated coagulation and/or damage to the blood vessels.

Apoptotic mimicry

Exposure of phosphatidylserine on the surface of a pathogen, thereby allowing its interaction with phosphatidylserine receptors on phagocytes to promote uptake and infection.

Macropinocytosis

An actin-driven endocytic process by which large, uncoated and fluid-filled vesicles are formed, thereby allowing the uptake of extracellular material (including viruses) into the cell.

Secretory pathway

A pathway composed of the endoplasmic reticulum, Golgi apparatus, lysosome and cell membrane (as well as the vesicles that transit between them) and responsible for the secretion of proteins into the extracellular environment.

Multivesicular bodies

A specialized type of late endosomes that contain internal membrane-bound vesicles formed by budding of the endosomal membranes into their lumen.

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Hoenen, T., Groseth, A. & Feldmann, H. Therapeutic strategies to target the Ebola virus life cycle. Nat Rev Microbiol 17, 593–606 (2019). https://doi.org/10.1038/s41579-019-0233-2

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