Nucleoside derivatives for treatment of
A method and composition for treating a host infected with a Caliciviridae virus, such as a Norovirus, comprising administering an effective treatment amount of a described modified nucleoside or a pharmaceutically acceptable salt thereof, is provided.
1. A method for treating infections caused by a Caliciviridae virus, comprising administering an effective treatment amount of a compound of the formula
acyl and phosphate ester prodrugs thereof, or pharmaceutically-acceptable salts thereof.
2. The method of claim 1 , wherein the virus is Norovirus or Saporovirus.
3. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered in combination or alternation with a second active agent.
4. The method of claim 3 , wherein the second active agent is selected from the group consisting of an interferon, a negatively charged glycosaminoglycan, a vitamin, lysine, an anti-emetic, an anti-diarrheal agent, and an analgesic.
5. The method of claim 4 , wherein the interferon is type I interferon (IFN).
6. The method of claim 4 , wherein the second antiviral agent is a negatively charged glycosaminoglycan.
7. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is in the form of a dosage unit.
8. The method of claim 7 , wherein the dosage unit contains 10 to 1500 mg of the compound and blood levels of 1-20 μM are achieved.
9. The method of claim 7 , wherein the dosage unit is a tablet or capsule.
10. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is in substantially pure form.
11. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is at least 90% by weight of the β-D-isomer or the β-L-isomer.
12. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is at least 95% by weight of the β-D-isomer or the β-L-isomer.
13. The method of claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt selected from the group consisting of a tosylate, methanesulfonate, acetate, citrate, malonate, tartrate, succinate, benzoate, ascorbate, α-ketoglutarate, α-glycerophosphate, formate, fumarate, propionate, glycolate, lactate, pyruvate, oxalate, maleate, salicylate, sulfate, nitrate, bicarbonate, carbonate salts, hydrobromate, hydrochloride, di-hydrochloride, and phosphoric acid salt.
14. The method of claim 13 , wherein the pharmaceutically acceptable salt is a hydrochloride salt.
15. The method of claim 1 , wherein the composition is administered topically, parenterally, or mucosally.
16. The method of claim 15 , wherein the mucosal administration is intranasal, oral, intrarectal, or intravaginal.
17. The method of claim 1 , wherein the compound is administered parenterally.
18. The method of claim 17 , wherein the parenteral administration is transcutaneous.
19. A method for treating a Caliciviridae infection, comprising administering an effective treatment amount of a compound of the formula:
acyl or phosphate ester prodrugs thereof, or a pharmaceutically-acceptable salt thereof to a patient exposed to, anticipated to be exposed to, or infected by, a Caliciviridae virus.
20. The method of claim 19 , wherein the virus is selected from the group consisting of Norovirus or Saporovirus.
21. The method of claim 19 , wherein the treatment method involves the co-administration of a compound of the formula:
a prodrug thereof, or a pharmaceutically-acceptable salt thereof, in combination and/or alternation with one or more additional therapeutic agents selected from the group consisting of an interferon, a negatively charged glycosaminoglycan, a vitamin, lysine, an anti-emetic, an anti-diarrheal agent, and an analgesic.