Methods and compositions for inhibition of polymerase
View Patent ↗The present invention is directed to methods and compositions for inhibition of viral nucleic acid polymerases, such as RNA and DNA polymerases, and methods and compositions that are useful for treating viral infections in subjects. The methods comprise administering to the subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or hydrate thereof, or a composition comprising a compound of formula I, or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier. The composition or method may optionally comprise one or more additional anti-viral agents.
1. A method for treating a viral infection, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt or hydrate thereof; wherein the virus is selected from the group consisting of viruses of the orthomyxoviridae, paramyxoviridae, arenaviridae, bunyaviridae, flaviviridae, filoviridae, togaviridae, picornaviridae, and coronaviridae families.
2. The method of claim 1 , wherein the virus is selected from the group consisting of rhinovirus, polio, measles, Ebola, Coxsackie, West Nile, yellow fever, Dengue fever, influenza A, influenza B, lassa, lymphocytic choriomeningitis, Junin, Machupo, guanarito, hantavirus, Rift Valley Fever, La Crosse, California encephalitis, Crimean-Congo, Marburg, Japanese Encephalitis, Kyasanur Forest, Eastern equine encephalitis, Western equine encephalitis, severe acute respiratory syndrome (SARS), parainfluenza, Tacaribe, and Pichinde viruses.
3. The method of claim 2 , wherein the subject is a human.
4. The method of claim 3 , wherein the virus is selected from the group consisting of rhinovirus, measles, Ebola, West Nile, yellow fever, Dengue fever, influenza A, influenza B, Junin, Rift Valley Fever, Marburg, SARS, parainfluenza, Tacaribe, and Pichinde viruses.
5. The method of claim 4 , wherein the virus is selected from the group consisting of Ebola, Marburg, yellow fever, influenza A, and influenza B viruses.
6. The method of claim 5 , wherein the virus is Ebola or Marburg virus.
7. The method of claim 6 , wherein the virus is Marburg virus.
8. The method of claim 4 , wherein the virus is West Nile virus.
9. The method of claim 4 , wherein the virus is yellow fever virus.
10. The method of claim 4 , wherein the virus is Dengue fever virus.
11. The method of claim 4 , wherein the virus is Rift Valley Fever virus.
12. The method of claim 3 , further comprising co-administering to the subject an effective amount of an anti-viral agent.
13. The method of claim 12 , wherein the anti-viral agent is a neuraminidase inhibitor.
14. The method of claim 12 , wherein the anti-viral agent is selected from the group consisting of laninamivir, oseltamivir, zanamivir, and peramivir.
15. The method of claim 12 , wherein the anti-viral agent is peramivir.
16. The method of claim 3 , wherein the compound is administered intravenously, intraperitoneally, intramuscularly, or orally.
17. A method for suppressing a viral infection, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt or hydrate thereof; wherein the virus is selected from the group consisting of viruses of the orthomyxoviridae, paramyxoviridae, arenaviridae, bunyaviridae, flaviviridae, filoviridae, togaviridae, picornaviridae, and coronaviridae families.
18. The method of claim 17 , wherein the virus is selected from the group consisting of rhinovirus, polio, measles, Ebola, Coxsackie, West Nile, yellow fever, Dengue fever, influenza A, influenza B, lassa, lymphocytic choriomeningitis, Junin, Machupo, guanarito, hantavirus, Rift Valley Fever, La Crosse, California encephalitis, Crimean-Congo, Marburg, Japanese Encephalitis, Kyasanur Forest, Eastern equine encephalitis, Western equine encephalitis, severe acute respiratory syndrome (SARS), parainfluenza, Tacaribe, and Pichinde viruses.
19. The method of claim 18 , wherein the subject is a human.
20. The method of claim 19 , wherein the virus is selected from the group consisting of rhinovirus, measles, Ebola, West Nile, yellow fever, Dengue fever, influenza A, influenza B, Junin, Rift Valley Fever, Marburg, SARS, parainfluenza, Tacaribe, and Pichinde viruses.
21. The method of claim 20 , wherein the virus is selected from the group consisting of Ebola, Marburg, yellow fever, influenza A, and influenza B viruses.
22. The method of claim 21 , wherein the virus is Ebola or Marburg virus.
23. The method of claim 22 , wherein the virus is Marburg virus.
24. The method of claim 20 , wherein the virus is West Nile virus.
25. The method of claim 20 , wherein the virus is yellow fever virus.
26. The method of claim 20 , wherein the virus is Dengue fever virus.
27. The method of claim 20 , wherein the virus is Rift Valley Fever virus.
28. The method of claim 19 , further comprising co-administering to the subject an effective amount of an anti-viral agent.
29. The method of claim 28 , wherein the anti-viral agent is a neuraminidase inhibitor.
30. The method of claim 28 , wherein the anti-viral agent is selected from the group consisting of laninamivir, oseltamivir, zanamivir, and peramivir.
31. The method of claim 28 , wherein the anti-viral agent is peramivir.
32. The method of claim 19 , wherein the compound is administered intravenously, intraperitoneally, intramuscularly, or orally.