Potential Therapeutic for Arthropod-borne Flaviviruses, such as Yellow Fever, Dengue and Zika Viruses
Princeton Docket # 18-3474
Researchers in the Department of Molecular Biology have discovered a human host factor that is required for effective yellow fever virus (YFV) infection of human cells. This molecule is unlike anything, in both structure and function, to what is known to regulate the life cycle of arthropod-borne flaviviruses. The potential compound has no reported cellular function therefore reducing the risks to the host which have been problematic in other targets investigated as potential therapeutics.
A highly specific inhibitor targeting the interactions between the YFV and this human molecule antagonize YFV infection, and potentially also other related arthropod-borne flaviviruses such as dengue, Zika and West Nile viruses. This research represent a powerful and promising therapeutic option for the clinical management of YFV infection and potentially of other flavivirus.
Potential inhibition or treatment of flaviviruses, such as
Specific inhibitor with no reported host cellular function
Acute, short-term use therefore minimizing potential side effects
Quick path to commercialization, a lead compound has been identified
Arthropod-borne flaviviruses, such as dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV) and Zika virus (ZIKV), cause significant health and economic concerns worldwide. YFV is transmitted by mosquitoes and has a fatal outcome in 20% to 50% of infected patients. Despite the availability of an effective vaccine, there is no specific treatment against YFV and recent reemergence events, especially in Brazil and Angola, have killed hundreds during the 2016-2018 period. This resurgence has occurred particularly in areas with historically low or no YFV activity and with low vaccination coverage, and have highlighted a significant risk for about 400 to 500 million unvaccinated persons worldwide. Furthermore, through international travel and human migration imported YFV cases have been reported in the Asia Pacific region, including China. These areas while home of the appropriate mosquito vectors and having the right climate have never been affected by YFV and are home to billions without pre-existing immunity to this virus. New mass vaccination campaigns are now facing important challenges, such as limited stock to respond to future outbreaks, effectiveness of vaccine fractional dose strategies, as well as reaching effective coverage in rural and isolated areas, more exposed to YFV.
Hence, effective therapeutic strategies allowing for the clinical managements of YFV infection cases would then represent powerful countermeasures to circumvent the challenges posed by vaccination, rapidly contain future outbreaks regardless of the vaccination coverage, and ultimately save lives.
Intellectual Property & Development Status
Princeton is currently seeking commercial partners and collaborators for the further development and commercialization of this opportunity.
Alexander Ploss, Ph.D., is an Associate Professor in the Department of Molecular biology at Princeton University. Dr. Ploss’s research focuses on immune responses and pathogenesis to human infectious diseases, including hepatitis viruses, related flaviviruses, and malaria. His group combines tissue engineering, molecular virology/pathogenesis, and animal construction, to create and apply innovative technologies including humanized mouse models for the study and intervention of human hepatotropic infections. In recognition of his work he received Astella’s Young Investigator Award from the Infectious Disease Society of America, a Liver Scholar Award from the American Liver Foundation, the Merck Irving Sigal Memorial Award from the American Society of Microbiology, the Löffler-Frosch Prize from the German Society of Virology, the Young Investigator Award from the Theobald Smith Society, the Research Scholar Award from the American Cancer Society, and an Investigator in Pathogenesis Award from the Burroughs Wellcome Fund. He is a member of the Genomic Instability and Tumor Progression Program at the Cancer Institute of NJ. Dr. Ploss completed his Bachelor’s and Master’s degree in biochemistry at the University of Tübingen, Germany including additional training the Howard Hughes Medical Institute at the University of Washington, Seattle, and at the German Cancer Research Center in Heidelberg, Germany. Dr. Ploss completed his Ph.D. in Immunology at Memorial Sloan-Kettering Cancer Center/Cornell University and postdoctoral training at the Rockefeller University. Prior to joining the Department of Molecular Biology at Princeton University in 2013, he was a research associate professor at the Center for the Study of Hepatitis C at the Rockefeller University.
Florian Douam, Ph.D., is a postdoctoral fellow in the Ploss laboratory
Qiang Ding, Ph.D., is a postdoctoral fellow in the Ploss laboratory
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