PAGE TITLE
Benzodiazepine compounds and screening assay for flavivirus antiviral therapeutics
PAGE SUMMARY
Researchers in the Baruch S. Blumberg Institute and Drexel’s Department of Microbiology & Immunology have developed an antiviral screening assay based on monitoring viral activation of host cell beta-interferon gene expression in a HEK293-derived reporter cell line expressing a luciferase gene under the control of a human interferon promoter. The readout of the reporter assay is the virus-induced host cellular innate immune response, allowing for identification of compounds that inhibit virus infection. Because interferon induction and the secretion of pro-inflammatory cytokines is a common host cell response to viral infection, the assay is widely applicable to virus types.
By implementing this screening assay from a library of 26,900 compounds, the researchers discovered a hit with a benzodiazepine compound that exhibited antiflavivirus activity, particularly against dengue virus and yellow fever virus. In subsequent development work, the researchers have demonstrated in vivo efficacy and safety of this inhibitor in an animal model of yellow fever. Although a vaccine exists for yellow fever, there is a need for effective antiviral therapeutics, as over 100,000 people are infected annually, and there is a high mortality rate among those infected.
APPLICATIONS
TITLE: Applications
Identification of compounds that inhibit viral infection
Use of benzodiazepine as therapy for flavivirus infection
ADVANTAGES
TITLE:Advantages
Assay gives direct measure of host cell immune response
Widely applicable to viruses that can infect reporter cell line and induce interferon expression
In vivo antiviral efficacy and safety demonstrated in animal model of yellow fever
IP STATUS
Intellectual Property and Development Status
Issued US patent 9,168,260
https://patents.google.com/patent/US9168260B2/en
PUBLICATIONS
References
Guo F. et al. A novel benzodiazepine compound inhibits yellow fever virus infection by specifically targeting the NS4B protein. Journal of Virology, 2016, 90(23).
http://jvi.asm.org/content/early/2016/09/15/JVI.01253-16.short?rss=1
Guo F. et al. An interferon-beta promoter reporter assay for high throughput identification of compounds against multiple RNA viruses. Antiviral Research, 2014, 107, p. 56-65.
http://www.sciencedirect.com/science/article/pii/S0166354214001168
Contact Information:
Robert McGrath
Sr. Associate Vice Provost
rbm26@drexel.edu