Synthetic catalase/superoxide dismutase mimetics and methods for treating viral infections
Inventors
Kash, John C. • Taubenberger, Jeffery K. • Levine, Rodney L. • Doctrow, Susan
Assignees
Boston University • US Department of Health and Human Services
Publication Number
US-10683316-B2
Publication Date
2020-06-16
Expiration Date
2032-11-09
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Abstract
The invention provides for the treatment of disorders related to viral infection, using salen manganese compounds.
Core Innovation
The invention provides methods of treating diseases or disorders associated with viral infection using salen manganese compounds, which act by providing protection against oxidative damage. The compounds have structural formulae specified as formula I and related variants, where the metal ion is selected from Mn, Mg, Co, Cu, Zn, V, Cr, or Ni, and various substituents are defined for rings and functional groups. The treatment involves administering an effective amount of these compounds or their pharmaceutically acceptable salts, esters, or hydrates to the subject in need.
The problem addressed is that viral infections, especially highly pathogenic ones such as the 1918 pandemic influenza virus, cause excessive oxidative stress and free radical generation, leading to oxidative damage to cells and tissues, lung pathology, and high mortality. Existing treatments do not adequately suppress oxidative stress or modulate the host inflammatory response to improve survival. Oxidative damage is a major contributing factor to the pathogenesis of viral infections, and controlling reactive oxygen species could be therapeutically beneficial.
Claims Coverage
The patent includes two main independent claims related to methods of treating pandemic influenza viral infection. The claims focus on identification of subjects with specific viral infections or symptomatology and administration of specific salen manganese compounds.
Method of treating pandemic influenza viral infection with salen manganese compounds
The method comprises identifying a subject with pandemic influenza viral infection exhibiting symptoms such as adult respiratory distress syndrome, severe necrotizing bronchitis, bronchiolitis, alveolitis, edema, or pulmonary hemorrhage, and administering to the subject an effective amount of a salen manganese compound of the specified formula.
Method of treating identified influenza viral infections with salen manganese compounds
The method comprises identifying a subject infected with an influenza virus subtype (including H1N1, H1N2, H2N2, H5N1, H7N7, or H9N2, particularly the 1918 pandemic influenza virus) and administering an effective amount of a salen manganese compound of the specified formula.
The independent claims cover methods of treating pandemic influenza viral infections by identifying infected subjects and administering salen manganese compounds, focusing on suppression of oxidative stress and targeting specific influenza subtypes including the 1918 virus, with modes of administration including oral and intraperitoneal routes.
Stated Advantages
Low cost of synthesis of the salen manganese compounds.
High stability of the compounds.
Low toxicity making them suitable for therapeutic use.
Capability to be formulated as aerosols for delivery.
Targeting host response pathways reduces likelihood of viral resistance development.
Broad specificity for treating multiple viral infections.
Documented Applications
Treatment or prophylaxis of influenza and pandemic influenza virus infections in humans and other animals susceptible to influenza.
Treatment of viral infections including but not limited to retrovirus, rhabdovirus, filovirus, hepatitis type A, B and C, herpes simplex types I and II, human immunodeficiency virus types I and II, human herpesvirus, and a broad range of other viruses described in detail.
Treatment of viral respiratory infections causing severe lung pathology such as necrotizing bronchitis, bronchiolitis, alveolitis, edema, and pulmonary hemorrhage.
Use in combination with standard antiviral agents including reverse transcriptase inhibitors, protease inhibitors, influenza-specific antiviral compounds, and other therapeutic agents for diseases caused by hepatitis B or HIV infections.
Protection from oxidative stress and mitochondrial injury during viral infections.
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