Emetine compounds for treatment and prevention of flavivirus infection
Inventors
Tang, Hengli • Lee, Emily M. • THARAPPEL, Anil Mathew • Song, Hongjun • Ming, Guo-li • Zheng, Wei • Xu, Miao • Yang, Shu • Huang, Ruili • HUANG, Wenwei • SHAMIM, Khalida • Li, Hao
Assignees
Florida State University Research Foundation Inc • Johns Hopkins University • US Department of Health and Human Services
Publication Number
US-10555942-B2
Publication Date
2020-02-11
Expiration Date
2038-10-10
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Abstract
The present invention concerns the use of emetine compounds for the treatment or prevention of Flavivirus infections, such as Zika virus infections. Aspects of the invention include methods for treating or preventing Flavivirus virus infection, such as Zika virus infection, by administering an emetine compound such as emetine or cephaeline, or a combination of two or more emetine compounds, to a subject in need thereof; methods for inhibiting Flavivirus infections such as Zika virus infections in a cell in vitro or in vivo; pharmaceutical compositions; packaged dosage formulations; and kits for treating or preventing Flavivirus infections, such Zika virus infections.
Core Innovation
The present invention concerns the use of emetine compounds for the treatment or prevention of Flavivirus infections, such as Zika virus infections. It includes methods for treating or preventing Flavivirus infections by administering emetine compounds, such as emetine or cephaeline, singly or in combination, to a subject in need thereof. The invention also relates to methods for inhibiting Flavivirus infections in vitro or in vivo, pharmaceutical compositions, packaged dosage formulations, and kits for treating or preventing Flavivirus infections.
The inventors have identified a novel use for emetine compounds in treating and preventing Zika virus (ZIKV) and other Flavivirus infections. The emetine compounds include emetine, cephaeline, psychotrine, o-methyl psychotrine, emetamine, cephaeline isoamyl ether, cephaeline ethyl ether, dehydroemetine, and various derivatives, prodrugs, metabolites, or pharmaceutically acceptable salts thereof. These compounds can be administered alone or in combination, and optionally with an additional agent useful for treating or preventing Flavivirus infection.
The problem being solved is the urgent need for effective therapies for Zika virus infection, a mosquito-borne flavivirus that has caused widespread outbreaks and is a growing public health concern globally. Unlike other arboviruses, ZIKV causes congenital defects such as microcephaly and is associated with Guillain-Barré syndrome. Thus, there is a significant need for methods and compositions to treat or prevent Zika virus and other Flavivirus infections.
Claims Coverage
The claims primarily focus on methods for treating or preventing Zika virus infection using cephaeline, detailing modes of administration, therapy or prophylaxis, diagnostic identification, and use with additional agents. Main inventive features are extracted from the independent claims.
Method for treating or delaying onset of Zika virus infection using cephaeline
A method comprising administering an effective amount of cephaeline, or a pharmaceutically acceptable salt thereof, to a subject in need thereof to treat or delay the onset of Zika virus infection.
Administering cephaeline as therapy upon infection diagnosis
The method wherein the subject has the Zika virus infection at time of administration, and cephaeline is administered as therapy, optionally after identifying the infection by assaying biological samples for Zika virus nucleic acids or proteins using RT-PCR, immunological assays, or PRNT.
Administering cephaeline as prophylaxis before infection
The method wherein the subject does not have Zika virus infection at administration, and cephaeline is administered to delay onset of infection.
Routes of administration for cephaeline
Administering cephaeline orally, nasally, rectally, parenterally, subcutaneously, intramuscularly, or intravascularly.
Combination administration with additional agents
Administering cephaeline together or separately with an additional agent effective for treating or delaying onset of Zika virus infection or symptoms thereof.
Method for inhibiting Zika virus infection in vitro or in vivo by contacting cells with cephaeline
Contacting an effective amount of cephaeline or a pharmaceutically acceptable salt thereof with human or non-human animal cells in vitro or in vivo before or after exposure to Zika virus to inhibit infection.
The claims cover methods of treatment and prevention of Zika virus infection using cephaeline, its administration for therapy or prophylaxis, modes of identifying infection, administration routes, combination therapies, and cell-based inhibition methods. The inventive features emphasize the use of cephaeline and its salts specifically for Zika virus treatment and prevention.
Stated Advantages
Emetine compounds inhibit or reduce Zika virus or other Flavivirus replication effectively in vitro and in vivo.
Combination of emetine compounds with emricasan or other compounds may have synergistic effects in protecting neural cells from virus-induced cell death.
Use of emetine compounds allows prophylactic or therapeutic treatment of Flavivirus infections, including multiple strains of Zika virus.
Documented Applications
Treatment or prevention of Flavivirus infections, including Zika virus infection in human or non-human animal subjects.
Inhibiting Flavivirus infection in cells in vitro or in vivo.
Use in combination with other agents useful for treating or preventing Flavivirus infections or symptoms thereof.
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