EBOV causes hemorrhagic fever often resulting in death. Because of its high mortality and ease of transmission from human to human, EBOV remains a biological threat for which effective preventive and therapeutic interventions are needed. In a study conducted by the VRC and published in Sci Transl Med. 2012 Feb 29;4(123):123ra24. doi: 10.1126/scitranslmed.3003500, it was demonstrated that productive replication of EBOV is modulated by c-Abl1 tyrosine kinase in vitro, and that a c-Abl specific kinase inhibitor (Nilotinib- Novartis), currently used to treat leukemia) prevents the release of Ebola virus-like particles and inhibits replication of the highly pathogenic Ebola Zaire strain by up to four orders of magnitude. This step of the virus life cycle may represent a target for developing antiviral therapeutics. In attempting to translate the in vitro findings to in vivo application and to standardize administration criteria (i.e. dose, route, species), we focused efforts on conducting non-GLP dose ranging and proof-of-principle studies. Through these studies we established an optimal animal model and drug delivery regimen to evaluate a possible therapeutic drugs protective efficacy against Ebola.
|García, Mayra; Cooper, Arik; Shi, Wei et al. (2012) Productive replication of Ebola virus is regulated by the c-Abl1 tyrosine kinase. Sci Transl Med 4:123ra24|
|Shi, Wei; Huang, Yue; Sutton-Smith, Mark et al. (2008) A filovirus-unique region of Ebola virus nucleoprotein confers aberrant migration and mediates its incorporation into virions. J Virol 82:6190-9|