Methods of treating and inhibiting Ebola virus infection
Inventors
Smith, Harold C. • Bennett, Ryan P. • Jahrling, Peter
Assignees
OYAGEN Inc • US Department of Health and Human Services
Publication Number
US-11617753-B2
Publication Date
2023-04-04
Expiration Date
2037-11-06
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Abstract
Disclosed herein are methods for treating an Ebola virus and inhibiting the transmission and propagation thereof.
Core Innovation
The invention provides methods for treating, preventing, and inhibiting the spread of Ebola virus infection using compounds having specific chemical Formula I and II, including sangivamycin and its analogs. These compounds can be administered as therapeutics in effective amounts to subjects infected or at risk of infection with various Ebola strains, such as Ivory Coast, Zaire, and Sudan Ebola viruses. The compounds inhibit Ebola virus propagation by targeting viral protein functions essential for viral replication and spread.
A key problem addressed by the invention is the formation and release of infectious Ebola viral particles mediated by the Ebola VP40 protein, which is essential for viral capsid assembly and viral particle formation at the plasma membrane of infected cells. Additionally, Ebola viral RNA polymerase (L protein) replicates the viral genome and transcribes viral RNA. Without effective treatment, Ebola virus replicates and spreads, causing severe infectious disease.
The invention solves these problems by providing compounds that inhibit the self-assembly of the Ebola VP40 protein, preventing the formation of virus-like particles and thus blocking viral particle release from infected cells. Furthermore, the compounds inhibit the activity of the Ebola viral RNA-dependent RNA polymerase, thereby reducing viral genome replication and transcription. By combining these modes of action, the disclosed compositions can treat Ebola virus infections, reduce viral spread, and potentially inhibit outbreak propagation.
Claims Coverage
The patent includes four independent claims focused on methods of preventing and treating Ebola virus infections using specific compounds, including sangivamycin and its analogs. The main inventive features relate to the chemical identity of the compounds and their therapeutic application against Ebola virus.
Use of compounds with specific chemical formula to prevent Ebola virus spread
A method for preventing Ebola virus infection in a subject at risk by contacting the subject with a therapeutically effective amount of a compound having Formula I, wherein the compound has specified substituents such as X chosen from O or S, and R1, R2 chosen among defined groups, or pharmaceutically acceptable salts thereof.
Treatment of Ebola virus infection with sangivamycin and related analogs
The use of compounds including sangivamycin and its derivatives (Formula IIIa through IIId), or pharmaceutically acceptable salts thereof, to treat an individual infected with an Ebola virus infection, where the compounds inhibit viral components essential for Ebola virus replication and assembly.
In summary, the claims cover methods for preventing and treating Ebola virus infections by administering therapeutically effective amounts of specific chemical compounds that inhibit Ebola virus VP40 protein assembly and RNA polymerase activity, thereby reducing viral replication and spread.
Stated Advantages
The compounds inhibit Ebola VP40 protein self-assembly, preventing formation of infectious viral particles.
The compounds inhibit Ebola viral RNA polymerase activity, thereby reducing viral genome replication and transcription.
The compounds can stop the spread of Ebola virus in a population and be used in combination therapy with other drugs.
The disclosed compounds exhibit dose-dependent antiviral activity at nanomolar concentrations with limited cytotoxicity.
Documented Applications
Treatment of human and animal subjects infected with one or more strains of Ebola virus, including but not limited to Ivory Coast, Zaire, and Sudan Ebola viruses.
Prophylactic treatment to prevent Ebola virus infection in subjects at risk or exposed to the virus.
Use in pharmaceutical compositions administered intravenously or intramuscularly in single doses ranging from 0.5 mg/kg to 50 mg/kg.
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