Nucleoside derivatives for treatment of Caliciviridae infections, including Norovirus infections
Inventors
Schinazi, Raymond F. • Whitaker, Richard Anthony • McBrayer, Tamara Rosario • Coats, Steven J.
Assignees
US Department of Veterans Affairs
Publication Number
US-8415321-B2
Publication Date
2013-04-09
Expiration Date
2029-04-09
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Abstract
A method and composition for treating a host infected with a Caliciviridae virus, such as a Norovirus, comprising administering an effective treatment amount of a described modified nucleoside or a pharmaceutically acceptable salt thereof, is provided.
Core Innovation
The invention provides compounds, pharmaceutical compositions, and methods for treating Caliciviridae infections, specifically Norovirus infections, by administering modified nucleoside compounds or their pharmaceutically acceptable salts. These compounds are substituted nucleosides of defined chemical formulas that demonstrate antiviral activity against Norovirus infection. The methods include treatment of infected hosts or prophylactic administration to prevent or reduce the spread of Norovirus.
Norovirus is a highly infectious virus in the Caliciviridae family causing significant gastroenteritis cases globally. It is transmitted mainly by fecal-oral routes and results in symptoms such as vomiting, diarrhea, and intestinal cramps with considerable morbidity and some mortality, especially among immunocompromised patients. Despite this, no approved pharmaceutical treatments currently exist for Norovirus infections, partly due to past difficulties in culturing the virus.
The invention addresses the unmet medical need by providing nucleoside analogs that inhibit viral replication, likely by targeting viral polymerase and/or helicase enzymes essential for Norovirus replication. The availability of replicon systems and in vitro infectivity assays facilitates screening and evaluation of these compounds. The invention also includes various prodrug and salt forms to optimize bioavailability and therapeutic efficacy, in addition to detailed synthesis methods and pharmaceutical formulations suited for oral or parenteral administration.
Claims Coverage
The patent contains two independent method claims focused on treating Caliciviridae infections using specified nucleoside derivative compounds.
Method for treating Caliciviridae infections with specified nucleoside compounds
Administering an effective treatment amount of a specific nucleoside derivative compound or its pharmaceutically acceptable salt to a host infected with a Caliciviridae virus, such as Norovirus or Saporovirus.
Method for treating Caliciviridae infections using an alternative specified nucleoside compound
Administering an effective treatment amount of another specific nucleoside derivative compound or its pharmaceutically acceptable salt to treat infections caused by Caliciviridae viruses, including Norovirus or Saporovirus.
The independent claims broadly cover therapeutic methods using particular nucleoside derivative compounds targeting Caliciviridae virus infections, including Norovirus and Saporovirus. They include variations in administration forms, enantiomeric purity, dosage, and co-administration with other agents to achieve treatment efficacy.
Stated Advantages
Provides novel chemical compounds and pharmaceutical compositions effective against Norovirus infections, addressing a significant unmet medical need.
Compounds can be used for treatment or prophylaxis, helping to prevent spread in high-risk populations and outbreak settings.
The invention enables potential inhibition of Norovirus viral polymerase and/or helicase, critical viral replication enzymes.
Offers various pharmaceutically acceptable prodrug and salt forms to improve bioavailability, stability, and administration flexibility.
Supports compatibility with high-throughput screening assays, facilitating drug discovery and optimization.
Documented Applications
Treatment of humans infected with Norovirus or other Caliciviridae viruses such as Saporovirus.
Prophylactic administration to individuals at risk of or exposed to Norovirus infection, such as in closed communities including hospitals, nursing homes, prisons, and cruise ships.
Use as monotherapy or in combination or alternation with other active agents including interferons, negatively charged glycosaminoglycans, vitamins, lysine, anti-emetics, anti-diarrheal agents, and analgesics.
Screening candidate compounds in high-throughput assays employing Norovirus replicon systems to identify antiviral activity.
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