Pharmaceutical compositions for the treatment of virus infection
The invention describes novel pharmaceutical compositions for the treatment of virus infections and cancer. The pharmaceutical compositions include mutant oligoadenylate synthetases (OAS) that have either enhanced cell permeability, reduced oxidative potential, improved antiviral activity, improved enzymatic activity, or absent enzymatic activity. The pharmaceutical compositions have improved drug properties and retain or have enhanced antiviral activity relative to their native forms. The pharmaceutical compositions further include chemically modified oligoadenylate synthetases, such chemical modifications being designed to increase serum stability and reduce immunogenicity in vivo. Such chemical modifications further increase drug stability and manufacturability in vitro. Compositions composed of more than ninety novel modifications are described. Also described are antibodies to polypeptides of the invention.
1. A method of treating a viral infection in a mammal in need thereof, comprising administering to said mammal a pharmaceutical composition comprising an antiviral but enzymatically inactive 2′,5′ oligoadenylate synthetase (OAS) polypeptide consisting of SEQ ID NO. 1 with up to two mutations at positions 75 and/or 77.
2. The method of claim 1 , wherein said up to two mutations replace alanine for aspartic acid.
3. The method of claim 1 wherein said viral infection is caused by a member of the Flaviviridae family, the Hepadnaviridae family, the Picornaviridae family, the Retroviridae family, the Coronaviridae family, the Rhabdoviridae family, the Paramyxoviridae family, the Papillomaviridae family, or the Herpesviridae family.
4. The method of claim 1 wherein said viral infection is caused by Hepatitis C Virus, Yellow Fever Virus, West Nile Virus, Japanese Encephalitis Virus, Dengue Virus, Bovine Viral Diarrhea Virus, Hepatitis B Virus, Encephalomyocarditis Virus, Human Rhinovirus, Hepatitis A Virus, Human Immunodeficiency Virus, Simian Immunodeficiency Virus, Human T-Lymphotropic Virus, Rous Sarcoma Virus, SARS coronavirus, Rabies Virus Vesicular Stomatitis Virus, Respiratory Syncytial Virus, Parainfluenza Virus, Human Papillomavirus, Influenza Virus, or Herpes Simplex Virus.
5. The method of claim 1 wherein said treating is therapeutic or prophylactic.