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
Florida State University Research Foundation Inc • University of Pennsylvania Penn • US Department of Health and Human Services
Publication Number
US-11779570-B2
Publication Date
2023-10-10
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 specific compounds and compositions for the treatment or prevention of Flavivirus infections, including dengue virus and Zika virus infections. The methods encompass administering these compounds to subjects in need, inhibiting Flavivirus infection in cells in vitro or in vivo, and providing pharmaceutical compositions, packaged dosage formulations, and kits containing the compounds.
The problem addressed arises from the absence of specific antiviral treatments for flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV). Current treatments are supportive rather than antiviral. Dengue virus has multiple serotypes causing varying disease severity without current specific antiviral therapies. Similarly, Zika has re-emerged as a significant health issue with congenital and neurological complications but lacks targeted antiviral treatment.
The invention utilizes a computational model based on a Zika NS-1 assay to predict anti-Flavivirus compounds. Since NS-1 protein expression occurs only during flavivirus replication, compounds inhibiting NS-1 indicate viral replication inhibition in human cells. The model identified 19 compounds that experimentally showed potent inhibition of NS-1 production and viral replication, enabling new therapeutic options for flavivirus infections.
Claims Coverage
The patent includes multiple independent claims focusing on methods and compositions involving compounds identified for treatment or inhibition of dengue or flavivirus infections. The inventive features cover novel antiviral compounds, methods of administration, and pharmaceutical compositions.
Method for inhibiting dengue virus infection in cells
A method comprising contacting human or non-human mammalian cells in vitro or in vivo, after dengue virus exposure, with a compound having a specific chemical structure to inhibit dengue virus infection.
The claims primarily cover methods of treating or preventing flavivirus infections, particularly dengue virus, by administering specific compounds identified by the invention. The claims also cover compositions and kits containing these antiviral compounds.
Stated Advantages
The compounds may be used to block flavivirus replication effectively by inhibiting NS-1 protein production during viral replication.
The use of the computational model enables identification and experimental validation of novel potent anti-flavivirus compounds.
Combinations of compounds may exhibit synergistic effects in protecting cells from flavivirus-induced cell death.
Prodrug and formulation approaches can improve solubility, targeting, bioavailability, and patient compliance.
Documented Applications
Treatment or prevention of flavivirus infections, including dengue virus and Zika virus infection, in human or non-human animals.
Inhibition of flavivirus infection in human or non-human animal cells in vitro or in vivo.
Use in pharmaceutical compositions, packaged dosage formulations, and kits for therapy or prophylaxis against flavivirus infections.
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