β-L-2′-deoxynucleosides for the treatment of resistant HBV strains and combination therapies
View Patent ↗It has been discovered that β-L-2′-deoxynucleosides are active against drug-resistant hepatitis B virus with mutations. A method for treating lamivudine resistant HBV (M552V) in a host is provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug. In addition, a method for preventing lamivudine resistant HBV (M552V) mutation from occurring in a naïve host is provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug. A method for preventing and/or suppressing the emergence of the HBV double mutant (L528M/M552V) in a host is also provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug.
1. A method for the treatment of a host infected with a drug-resistant form of HBV, said HBV exhibiting a mutation at the 552 codon from methionine to valine in the DNA polymerase region, said method comprising administering an effective amount of a β-L-2′-deoxynucleoside having thymine or cytosine as base, or a pharmaceutically acceptable salt, ester or prodrug thereof.
2. The method of claim 1 wherein the β-L-2′-deoxynucleoside has the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof.
3. The method of claim 2 wherein the β-L-2′-deoxynucleoside is in the form of a pharmaceutically acceptable ester.
4. The method of claim 2 wherein the β-L-2′-deoxynucleoside is in the form of a pharmaceutically acceptable salt.
5. The method of claim 2 wherein the β-L-2′-deoxynucleoside is in the form of a pharmaceutically acceptable prodrug.
6. The method of claim 2 wherein the host is a mammal.
7. The method of claim 2 wherein the host is a human.
8. The method of claim 2 wherein the drug-resistant form of HBV is a lamivudine resistant form of HBV.