Compositions and methods for inhibiting entry of a hepatic virus
View Patent ↗The present invention embraces Niemann-Pick C1-like 1 protein antagonists and agents that inhibit hepatic virus infection for use in the prevention and treatment of a hepatic virus infection.
1. A method for reducing or preventing entry of a hepatic virus into a cell comprising contacting a hepatic cell in the presence of a hepatic virus with an effective amount of a Niemann-Pick C1-like 1 protein antagonist that reduces or prevents entry of hepatic virus into the cell.
2. The method of claim 1 , wherein the Niemann-Pick C1-like 1 protein antagonist is an azetidinone-based cholesterol absorption inhibitor.
3. The method of claim 2 , wherein the azetidinone-based cholesterol absorption inhibitor is ezetimibe, a phenolic glucuronide derivative of ezetimibe, (+)-7-(4-chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-3R-(4-hydroxyphenyl)-2-azaspiro[3,5]nonan-1-one) or (3R)-3 phenylpropyl)-1,(4S)-bis(4-methoxyphenyl)-2-azetidinone.
4. A method for preventing a hepatic virus infection of the liver comprising administering to a subject at risk of a hepatic virus infection of the liver an effective amount of a Niemann-Pick C1-like 1 protein antagonist that reduces or prevents entry of hepatic virus into cells of a liver thereby preventing a hepatic virus infection of the liver.
5. The method of claim 4 , wherein the subject has had a liver transplant.
6. The method of claim 4 , wherein the Niemann-Pick C1-like 1 protein antagonist is an azetidinone-based cholesterol absorption inhibitor.
7. The method of claim 6 , wherein the azetidinone-based cholesterol absorption inhibitor is ezetimibe, a phenolic glucuronide derivative of ezetimibe, (+)-7-(4-chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-3R-(4-hydroxyphenyl)-2-azaspiro[3,5]nonan-1-one) or (3R)-3 phenylpropyl)-1,(4S)-bis(4-methoxyphenyl)-2-azetidinone.
8. A method for effecting clearance of hepatic virus from a cell comprising contacting a cell infected with a hepatic virus with an effective amount of a synergistic composition including a Niemann-Pick C1-like 1 protein antagonist and at least one other agent that inhibits hepatic virus infection so that the hepatic virus is cleared.
9. The method of claim 8 , wherein the Niemann-Pick C1-like 1 protein antagonist is an azetidinone-based cholesterol absorption inhibitor.
10. The method of claim 9 , wherein the azetidinone-based cholesterol absorption inhibitor is ezetimibe, a phenolic glucuronide derivative of ezetimibe, (+)-7-(4-chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-3R-(4-hydroxyphenyl)-2-azaspiro[3,5]nonan-1-one) or (3R)-3 phenylpropyl)-1,(4S)-bis(4-methoxyphenyl)-2-azetidinone.
11. The method of claim 8 , wherein the at least one other agent that inhibits hepatic virus infection is a type I interferon.
12. The method of claim 11 , wherein the type I interferon (IFN) is IFN-α or IFN-β.
13. A method for treating a hepatic virus infection comprising administering to a subject with a hepatic virus infection an effective amount of a synergistic composition including a Niemann-Pick C1-like 1 protein antagonist and at least one other agent that inhibits hepatic virus infection so that the hepatic virus infection is treated.
14. The method of claim 13 , wherein the Niemann-Pick C1-like 1 protein antagonist is an azetidinone-based cholesterol absorption inhibitor.
15. The method of claim 14 , wherein the azetidinone-based cholesterol absorption inhibitor is ezetimibe, a phenolic glucuronide derivative of ezetimibe, (+)-7-(4-chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-3R-(4-hydroxyphenyl)-2-azaspiro[3,5]nonan-1-one) or (3R)-3 phenylpropyl)-1,(4S)-bis(4-methoxyphenyl)-2-azetidinone.
16. The method of claim 13 , wherein the at least one other agent that inhibits hepatic virus infection is a type I interferon.
17. The method of claim 16 , wherein the type I interferon (IFN) is IFN-α or IFN-β.