Method for inhibiting dengue virus infection
Inventors
Tang, Hengli • Lee, Emily M. • Zheng, Wei • Huang, Ruili • Xu, Miao • HUANG, Wenwei • SHAMIM, Khalida • Ming, Guoli • Song, Hongjun
Assignees
Unites States Of America Represented By Secretary Department Of Health And Human Services AS • Florida State University Research Foundation Inc • University of Pennsylvania Penn • US Department of Health and Human Services
Publication Number
US-11903929-B2
Publication Date
2024-02-20
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 provides compounds and compositions for the treatment or prevention of Flavivirus infections, including dengue virus and Zika virus infections. Methods are disclosed for treating or preventing these infections by administering specific compounds or compositions to subjects in need, as well as methods for inhibiting Flavivirus infections in cells both in vitro and in vivo. Pharmaceutical compositions, packaged dosage forms, and kits useful for treating or preventing Flavivirus infections are also provided.
The problem addressed by the invention arises from the lack of approved antiviral treatments for dengue virus (DENV) or Zika virus (ZIKV) infections. These viruses present significant public health concerns, with dengue fever causing severe and life-threatening syndromes and Zika virus associated with congenital defects and neurological disorders. Current therapies are primarily supportive, leaving a need for effective antiviral agents.
The invention includes identifying compounds that inhibit flavivirus NS-1 protein production, which is only expressed during viral replication. Inhibition of NS-1 indicates the compounds block virus replication in human cells. Nineteen specific compounds were identified by a computational model and experimentally validated to inhibit NS-1 production and viral replication. These compounds, or their prodrugs, metabolites, derivatives, or pharmaceutically acceptable salts, may be used therapeutically or prophylactically to treat or prevent infections by Flaviviruses such as dengue virus and Zika virus.
Claims Coverage
The patent includes one independent claim focusing on a method for inhibiting dengue virus infection in mammalian cells using a compound with a specific chemical structure.
Method for inhibiting dengue virus infection in cells
A method for inhibiting dengue virus infection in human or non-human mammalian cells in vitro or in vivo by contacting the cells with a compound having a specific chemical structure after exposure of the cells to the dengue virus.
The claims cover a method of inhibiting dengue virus infection using compounds with defined chemical structures applied to mammalian cells either in vitro or in vivo, characterizing a novel antiviral approach.
Stated Advantages
The compounds block flavivirus replication by inhibiting NS-1 protein production, demonstrating antiviral activity against dengue virus and Zika virus.
The compounds may be used therapeutically to treat existing infections or prophylactically to prevent infection.
Pharmaceutical compositions, dosage formulations, and kits facilitate effective administration and patient compliance.
Documented Applications
Treatment or prevention of Flavivirus infections, including dengue virus infection of any serotype and Zika virus infection, in human or non-human animal subjects.
Inhibition of Flavivirus infections in human or non-human animal cells in vitro or in vivo.
Use of specific compounds or combinations thereof as antiviral agents against dengue virus and Zika virus.
Administration of compounds as therapy to subjects with flavivirus infection or prophylactically to prevent or delay onset of infection.
Formulation of the compounds into pharmaceutical compositions, packaged dosage formulations, and kits for clinical use.
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