Anti-flavivirus compounds and methods of use
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-11471443-B2
Publication Date
2022-10-18
Expiration Date
2039-12-19
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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 compounds and compositions for the treatment or prevention of Flavivirus infections, including dengue virus and Zika virus infections. The compounds inhibit the flavivirus NS-1 protein production, which is expressed only during the virus replication stage, indicating that these compounds inhibit virus replication in human cells. The invention includes methods of treating or preventing flavivirus infection by administering these compounds or compositions to subjects, methods for inhibiting flavivirus infection in cells in vitro or in vivo, pharmaceutical compositions, packaged dosage formulations, and kits useful for such treatment or prevention.
A computational model based on flavivirus Zika NS-1 assay data predicted 19 compounds with anti-flavivirus activity, which were experimentally verified to inhibit NS-1 production and block viral replication in human cells. These compounds, and their prodrugs, metabolites, derivatives, or pharmaceutically acceptable salts, are disclosed in the invention. The compounds may be administered individually or in combination, and optionally with additional biologically active agents. The compounds can be formulated into various pharmaceutical compositions and dosage forms for effective administration via multiple routes including oral, nasal, rectal, parenteral, subcutaneous, intramuscular, or intravascular.
The compounds inhibit flavivirus infections such as dengue virus (all serotypes) and Zika virus infections, both as therapy in infected subjects and as prophylaxis to prevent or delay onset of infection. Methods to identify infected subjects prior to administration include testing biological samples for flavivirus nucleic acids or proteins using assays such as RT-PCR, immunological assays, or plaque-reduction neutralization testing. The invention also contemplates derivatives of the compounds prepared via various standard chemical reactions and modifications to improve bioavailability and pharmacokinetic properties.
Claims Coverage
The patent claims cover several inventive features related to methods of treating and inhibiting flavivirus infections, pharmaceutical compositions, dosage formulations, and kits involving specific anti-flavivirus compounds.
Methods for treating flavivirus infection with specific compounds
The claims include methods for treating flavivirus infection in human or non-human subjects by administering an effective amount of compounds having defined chemical structures, including treatment of dengue virus and Zika virus infections.
Methods for identifying flavivirus infection prior to treatment
The claims encompass identifying subjects as having flavivirus infection prior to administration of compounds by assaying biological samples for dengue or Zika virus nucleic acids or proteins using techniques such as RT-PCR, immunological assays, or plaque-reduction neutralization testing.
Various administration routes and formulations for anti-flavivirus compounds
The claims provide for administration of the compounds orally, nasally, rectally, parenterally, subcutaneously, intramuscularly, or intravascularly, optionally with additional therapeutic agents in the same or separate formulations.
Methods for inhibiting flavivirus infection in mammalian cells in vitro or in vivo
The claims cover applying compounds to human or non-human mammalian cells before or after flavivirus exposure to inhibit infection, both in vitro and in vivo.
In summary, the claims define methods of using specific chemical compounds to treat or inhibit flavivirus infections including Zika and dengue viruses, methods for infection identification, various administration routes, and pharmaceutical formulations encompassing these compounds.
Stated Advantages
The compounds identified inhibit flavivirus NS-1 protein production, thereby blocking virus replication in human cells.
The identified compounds have potent anti-flavivirus activity against both Zika virus and dengue virus infections.
The invention provides both therapeutic and prophylactic uses for flavivirus infections, supporting flexible treatment strategies.
The compounds can be administered via multiple routes and formulated with pharmaceutical carriers enhancing delivery and bioavailability.
Documented Applications
Treatment or prevention of flavivirus infections such as Zika virus and dengue virus infections in human or non-human animal subjects.
Inhibiting flavivirus infection in human or non-human mammalian cells in vitro or in vivo, including before or after exposure to flavivirus.
Use in pharmaceutical compositions, packaged dosage formulations, and kits for treating or preventing flavivirus infections.
Use as therapy for subjects with flavivirus infections or prophylactically to prevent or delay infection onset.
Interested in licensing this patent?