Therapeutic strategies to target the Ebola virus life cycle

• Published in: Nature reviews. Microbiology 2019-10, Vol.17 (10), p.593-606
• Main Authors: Hoenen, Thomas, Groseth, Allison, Feldmann, Heinz
• Format: Article
• Language: English
• Subjects: 631/250/255/2514; 631/326/596/2042; 631/326/596/2555; 631/326/596/2557; Analysis; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Biomedical and Life Sciences; Congo (Kinshasa); Drug Evaluation, Preclinical - methods; Ebola virus; Ebola virus infections; Ebolavirus; Ebolavirus - drug effects; Ebolavirus - growth & development; Epidemics; Gene expression; Health aspects; High-throughput screening; Host-Pathogen Interactions - drug effects; Infection; Infectious Diseases; Life cycles; Life Sciences; Marburg virus disease; Medical Microbiology; Microbiology; Monoclonal antibodies; Morphogenesis; Parasitology; Review Article; Ribonucleic acid; RNA; RNA viruses; Synthesis; Transcription; Viral diseases; Virology; Virus diseases; Viruses
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/s41579-019-0233-2

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. In this Review, Hoenen, Groseth and Feldmann address strategies that have shown promise in interfering with the filovirus life cycle, including the entry process, viral RNA synthesis and gene expression, as well as morphogenesis and budding.