Inhibitors of serine protease activity and their use in methods and compositions for treatment of bacterial infections
AssigneeThe Regents of the University of Colorado
InventorLeland Shapiro
Life of this patent
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Abstract
A novel method of treating and preventing viral infection is provided. In particular a method of blocking viral infection facilitated by a serine proteolytic (SP) activity is disclosed, which consists of administering to a subject suffering or about to suffer from viral infection a therapeutically effective amount of a compound having a serine protease inhibitory or serpin activity. Among compounds are α1-antitrypsin (AAT), peptide derivatives from the carboxyterminal end of AAT, and man-made, synthetic compounds mimicking the action of such compounds. The preferred viral infections include retroviral infection such as human immunodeficiency virus (HIV) infection.
Claims45
A method of treating a subject suffering from a viral infection that is mediated by endogenous host serine protease (SP) or SP-like activity, which comprises administering to the subject a therapeutically effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity.
A method of inhibiting in a mammal the spread or onset of a viral infection that is mediated by endogenous host serine protease (SP) or SP-like activity, which comprises administering a therapeutically effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity to a mammalian subject exposed or at risk of potential exposure to an agent of a viral infection that is mediated by endogenous SP or SP-like activity.
A method of treating a patient with a deficiency of functional endogenous AAT levels and suffering from a viral infection that is mediated by an endogenous host serine protease (SP) or SP-like activity, which comprises administering to such a patient a therapeutically effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity.
A method of treating a subject suffering from a viral infection that is mediated at least in part by serine protease activity, comprising:
- administering to the subject a therapeutically effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity.
A method of inhibiting HIV replication in a subject harboring HIV which comprises administering to the subject a therapeutically effective amount of a substance exhibiting a binding affinity to a ligand binding domain of a SEC receptor.
A method of treating a subject suffering from a pathological condition that is mediated by endogenous serine protease (SP) or SP-like activity, which comprises administering to the subject a therapeutically effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity.
A method of preventing or inhibiting entry of viral nucleic acid into the nucleus of a mammalian host cell, which comprises administering an effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity to a mammalian host exposed or at risk of potential exposure to an agent of a viral infection that is mediated by endogenous host serine protease (SP) or SP-like activity.
A method of preventing or inhibiting the exit of a virion particle from a mammalian host cell harboring an agent of a viral infection that is mediated by endogenous host serine protease (SP) or SP-like activity, which comprises administering a pharmacologically effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity to such a mammalian host.
A method of preventing a deficiency of functional endogenous AAT levels in a mammalian patient susceptible to a viral infection that is mediated by endogenous host serine protease (SP) or SP-like activity, which comprises administering to such a mammalian patient a therapeutically effective amount of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity.
A pharmaceutical composition comprising effective amounts of a substance exhibiting mammalian α1-antitrypsin (AAT) or AAT-like activity and a pharmaceutically acceptable carrier.
A method for treating HIV infection in a host harboring said HIV comprising administering to the host a therapeutically effective combination of at least one of the compounds exhibiting AAT or AAT-like activity and one or more compounds selected from a group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors.
A pharmaceutical composition for treating HIV in a human host comprising an antivirally effective amount of a substance with AAT-like activity and physiologically acceptable salts thereof as an active ingredient, and a pharmaceutically acceptable carrier.
A pharmaceutical composition for treating HIV in a human host comprising an antivirally effective amount of a peptide having a general formula:
- I-A-B-C-D-E-F-G-H-II, wherein I is Cys or absent;
- A is Ala, Gly, Val or absent;
- B is Ala, Gly, Val, Ser or absent;
- C is Ser, Thr or absent;
- D is Ser, Thr, Ans, Glu, Arg, Ile, Leu or absent;
- E is Ser, Thr, Asp or absent;
- F is Thr, Ser, Asn, Gln, Lys, Trp or absent;
- G is Tyr or absent;
- H is Thr, Gly, Met, Met(O), Cys, Thr or Gly;, and II is Cys, an amide group, substituted amide group, an ester group or absent, wherein the peptide comprises at least 4 amino acids and physiologically acceptable salts thereof as an active ingredient, and a pharmaceutically acceptable carrier.
A pharmaceutical composition for treating HIV in a human host comprising an antivirally effective amount of a compound mimicking AAT activity as an active ingredient, and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.