Inhibition of dengue infection by binding of drugs to a novel site on dengue E protein.
Inventors: Stephen Harrison, Yorgo Modis
Invention Types: Therapeutics
Research Areas: Infectious Disease
Keywords: Drug Discovery, Drug Screening, Drug DesignFor More Information Contact: Meyer, Abbie
This invention identifies novel druggable regions in viral class II E proteins; the modulation of activity of such regions could inhibit fusion and, hence, infectivity. The invention also provides methods of screening compounds against the druggable regions in order to discover candidate therapeutics. A better understanding of the structure and activity of class II envelope fusion proteins and potentially druggable regions within will further the development of anti-viral fusion inhibitors for flaviviruses, alphaviruses, and hepatitis viruses.
Inhibition of viral fusion by small molecule drugs is a promising treatment or prophylactic, as has been demonstrated by anti-HIV fusion inhibitors. Success in inhibition of Dengue virus fusion could lead to similar success against other related flaviviruses infections (such as yellow fever and West Nile), alphaviruses (such as Sindbis and Semliki Forest viruses), as well as Hepatitis C. Present invention could be used in Drug Designing, Drug Discovery and Drug Screening.
Currently, there is no known cure or vaccine for Dengue fever and infection rates are rapidly increasing. There is no specific treatment for infection, and control of dengue virus by vaccination has proven elusive.
Dengue fever affects about 50 million people across five continents, and is spreading into the southern United States. Estimates suggest that over one-half million victims, many of whom are children, require hospitalization annually. Boston Children's hospital is looking to Exclusive/Non-Exclusive license this technology for development.
Key Publications: • Modis Y, et al. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci USA. 2003 Jun 10;100(12):6986-91.
• Modis Y, et al. Structure of the dengue virus envelope protein after membrane fusion. Nature. 2004 Jan 22;427(6972):313-9.
• Modis Y, et al. Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein. J Virol. 2004 Jan;79(2):1223-31.
• Schmidt AG, et al. Small-molecule inhibitors of dengue-virus entry. PLoS Pathog. 2012;8(4):e1002627.
• Klein DE, et al. Structure of a dengue virus envelope protein late-stage fusion intermediate. J Virol. 2013 Feb;87(4):2287-93.