Thiazolide compounds for treating viral infections
Inventors
Rossignol, Jean-Francois • Santoro, Maria Gabriella
Assignees
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Publication Number
US-11135202-B2
Publication Date
2021-10-05
Expiration Date
Abstract
Thiazolide compounds, such as nitazoxanide and/or tizoxanide, may be used against viruses belonging to the Picornaviridae family or the Paramyxoviridae family.
Core Innovation
The invention concerns thiazolide antivirals, including nitazoxanide and tizoxanide, and related thiazolides such as RM-4848 and RM-5038, for viral diseases associated with Picornaviridae and Paramyxoviridae. For Paramyxoviridae, the described activity is associated with reducing viral F glycoprotein maturation and intracellular translocation, including inhibition of transport to the cell surface.
The document describes that reducing intracellular mature F protein levels is accompanied by insolubilization and/or aggregation of the F protein. Mechanistic protein analyses are described using fractionation to assess insoluble versus soluble protein and localization approaches to support intracellular effects on immature and mature F protein.
The disclosed approach is presented as treatment of diseases having as a sole cause the relevant virus family, including monotherapy and also as an adjunct in combination with direct-acting antivirals and, in one context, with the neuraminidase inhibitor oseltamivir. The document further describes symptom-related endpoints and concentration metrics for activity in vitro in contexts that include respiratory syncytial virus and enterovirus/rhinovirus.
Claims Coverage
The partial content contains two independent claims. Across the independent claims, the main inventive elements are the use of a thiazolide compound within a specified dosing range, constrained to monotherapy, for diseases or conditions having Rhinovirus A as the sole cause, and tied to specific symptom definitions and treatment outcomes.
Monotherapy thiazolide for Rhinovirus A to reduce symptom duration
Administering 500 mg to 700 mg of a thiazolide compound selected from nitazoxanide, tizoxanide and a combination thereof or a pharmaceutically acceptable salt thereof as a monotherapy for a disease or condition having as a sole cause Rhinovirus A, wherein the administering provides a reduction of a duration of at least one symptom compared to an average duration in an untreated patient population.
Monotherapy thiazolide for Rhinovirus A based on respiratory symptom treatment
Treating a disease or condition having as a sole cause Rhinovirus A by administering 500 mg to 700 mg of a thiazolide compound selected from nitazoxanide, tizoxanide and a combination thereof or a pharmaceutically acceptable salt thereof as a monotherapy, wherein the subject has at least one respiratory symptom selected from cough, nasal obstruction and sore throat.
Both independent claims cover monotherapy with nitazoxanide and/or tizoxanide, or a combination or pharmaceutically acceptable salt, at 500 mg to 700 mg for diseases or conditions caused solely by Rhinovirus A. The first independent claim additionally requires reduction of symptom duration compared to an untreated-population average, while the second independent claim focuses on subjects presenting with respiratory symptoms selected from cough, nasal obstruction, and sore throat.
Stated Advantages
Reduction of the duration of at least one symptom in treated subjects compared to an untreated patient population average.
Documented Applications
Reducing the duration of symptoms of a disease or condition having Rhinovirus A as a sole cause, for symptoms including fever, feverishness, headache, myalgia, fatigue, cough, nasal obstruction and sore throat.
Treating a disease or condition having Rhinovirus A as a sole cause in subjects with respiratory symptoms selected from cough, nasal obstruction and sore throat.
Antiviral use of thiazolide compounds, including nitazoxanide, tizoxanide, RM-4848 and RM-5038, for viral families including Picornaviridae and Paramyxoviridae, with described intracellular effects on Paramyxoviridae F glycoproteins.
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