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-11096927-B2
Publication Date
2021-08-24
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
Flaviviruses, including dengue virus and Zika virus, cause significant human diseases and currently lack approved antiviral treatments; existing therapies are only supportive. The invention addresses this unmet medical need by identifying compounds that can treat or prevent Flavivirus infections, thereby filling a critical gap in antiviral therapy.
A computational model based on data from the flavivirus Zika NS-1 assay was developed to predict anti-Flavivirus compounds. Since the NS-1 protein is produced only during the virus replication stage, compounds that inhibit NS-1 production indicate inhibition of viral replication in human cells. Using this model, 19 compounds were identified and experimentally validated as potent inhibitors of NS-1 production and viral replication in human cells.
The invention encompasses these 19 compounds and their prodrugs, metabolites, derivatives, and pharmaceutically acceptable salts. It includes their use in compositions, dosage formulations, and kits, as well as methods for treating or preventing flavivirus infection in subjects in need thereof by administering these compounds. It also covers methods for inhibiting Flavivirus infection in cells in vitro or in vivo by contacting the cells with these compounds.
Claims Coverage
The patent contains two main independent claims covering methods of treatment and infection inhibition using a specific compound and its forms. The following inventive features are derived from these independent claims.
Use of colchicine and its derivatives to treat Flavivirus infections
A method for treating a Flavivirus infection in a human or non-human mammalian subject comprising administering an effective amount of colchicine, a prodrug of colchicine, a metabolite of colchicine, or a pharmaceutically acceptable salt thereof, to a subject having dengue virus or Zika virus infection.
Use of colchicine and its derivatives to inhibit Flavivirus infection in cells
A method for inhibiting Flavivirus infection in human or non-human mammalian cells in vitro or in vivo by contacting the cells with an effective amount of colchicine, a prodrug, metabolite, or pharmaceutically acceptable salt thereof, after exposure to dengue virus or Zika virus infection.
The claims cover therapeutic and prophylactic methods utilizing colchicine and its related compounds to treat or inhibit dengue and Zika virus infections in subjects and cells, emphasizing the compound's antiviral application against Flavivirus infections.
Stated Advantages
The compounds inhibit flavivirus NS-1 protein production, which corresponds to effective viral replication inhibition in human cells.
The use of a computational model enables identification and experimental verification of potent anti-flavivirus compounds.
The disclosed compounds can be formulated into various pharmaceutical compositions, including prodrugs, derivatives, and salts, allowing flexible administration routes and improved bioavailability.
Combination therapies with multiple compounds or additional biologically active agents may provide synergistic antiviral effects.
Documented Applications
Treatment or prevention of flavivirus infections, specifically dengue virus infection and Zika virus infection, in human or non-human animal subjects at risk or already infected.
Inhibition of flavivirus infection in human or non-human animal cells in vitro or in vivo by contacting the cells with effective amounts of the disclosed compounds.
Use in pharmaceutical compositions, packaged dosage formulations, or kits for administering the compounds to treat or prevent flavivirus infections.
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