Method for inhibiting Zika virus infection
Inventors
Tang, Hengli • Lee, Emily M. • Zheng, Wei • Huang, Ruili • Xu, Miao • HUANG, Wenwei • SHAMIM, Khalida • Ming, Guoli • Song, Hongjun
Assignees
Florida State University Research Foundation Inc • University of Pennsylvania Penn • US Department of Health and Human Services
Publication Number
US-11850236-B2
Publication Date
2023-12-26
Expiration Date
2039-12-19
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Abstract
The present invention concerns the use of compounds and compositions for the treatment or prevention of Flavivirus infections, such as dengue virus infections and Zika virus infections. Aspects of the invention include methods for treating or preventing Flavivirus virus infection, such as dengue virus and Zika virus infection, by administering a compound or composition of the invention, to a subject in need thereof; methods for inhibiting Flavivirus infections, such as dengue virus and Zika virus infections, in a cell in vitro or in vivo; pharmaceutical compositions; packaged dosage formulations; and kits useful for treating or preventing Flavivirus infections, such as dengue virus and Zika virus infections.
Core Innovation
The invention concerns the use of compounds and compositions for the treatment or prevention of Flavivirus infections, including dengue virus and Zika virus infections. It develops methods for treating or preventing these infections by administering specific compounds to a subject in need thereof, as well as methods for inhibiting Flavivirus infections in human or non-human cells both in vitro and in vivo. The invention also includes pharmaceutical compositions, packaged dosage formulations, and kits useful for treating or preventing Flavivirus infections.
The problem addressed is that Flaviviruses such as Dengue virus and Zika virus are significant human pathogens with no approved antiviral treatments currently available, only supportive therapies. Zika virus has re-emerged recently causing public health concerns due to its association with congenital defects and Guillain-Barré syndrome. Similarly, Dengue virus poses a global health threat with various serotypes causing disease ranging from mild fever to severe, life-threatening syndromes, and there is no specific antiviral treatment. Thus, effective antiviral agents against these viruses are urgently needed.
The invention uses a computational model based on data from the flavivirus Zika NS-1 assay to predict new anti-Flavivirus compounds, which inhibit the NS-1 protein that is only synthesized during flavivirus replication. Nineteen compounds were identified that inhibit NS-1 production and block viral replication in human cells. These compounds, or their prodrugs, metabolites, derivatives, or pharmaceutically acceptable salts, can be formulated into compositions and used in methods for treating or preventing flavivirus infections such as dengue and Zika virus infections.
Claims Coverage
The claims include one independent claim that covers a method for inhibiting Zika virus infection using a specific compound with a defined chemical structure. The inventive features relate to the method steps, the mode of application, and the composition of the compound used in the method.
Method for inhibiting Zika virus infection by compound contacting
A method of inhibiting Zika virus infection in human or non-human mammalian cells, either in vitro or in vivo, by contacting the cells with a compound having a specific chemical structure after exposure to the Zika virus.
Mode of contacting cells with the compound
The method includes contacting the cells with the compound either in vitro or in vivo as alternative embodiments.
Application to human or non-human mammalian cells
The method encompasses contacting both human cells and non-human mammalian cells with the compound for inhibiting viral infection.
The claims focus on a method of inhibiting Zika virus infection by using a specific compound, detailing the mode of contact with cells, and covering application to human or non-human mammalian cells both in vitro and in vivo.
Stated Advantages
The compounds inhibit NS-1 protein production, indicating inhibition of virus replication in human cells, thus acting as potent anti-Flavivirus agents.
The combination of compounds may exhibit a synergistic effect in protecting cells from flavivirus-induced cell death.
Prodrug formulations and derivatives can enhance solubility, bioavailability, selective targeting, reduce toxic effects, and improve patient compliance.
Compounds can be administered through various routes, including oral, nasal, parenteral, subcutaneous, intramuscular, and intravenous, allowing flexible therapeutic use.
Documented Applications
Treatment or prevention of Flavivirus infections in humans or non-human animals, including infections caused by Zika virus, dengue virus, West Nile virus, tick-borne encephalitis virus, Japanese encephalitis virus, St. Louis encephalitis virus, and yellow fever virus.
Use of the compounds for prophylaxis to prevent or delay the onset of flavivirus infections or as therapy to treat existing flavivirus infections.
Methods for inhibiting flavivirus infection in cells in vitro or in vivo by contacting cells with the compounds before or after viral exposure.
Formulation of pharmaceutical compositions, packaged dosage forms, and kits comprising the compounds for therapeutic or prophylactic use against flavivirus infections.
Use in subjects including males, females, post-pubescent females, pregnant females, and subjects with conditions associated with Zika virus infection such as Guillain-Barré syndrome.
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