Pyrazolo[1,5]pyrimidine-based compounds and methods of their use to treat viral infections
Provided herein are methods of treating, managing and/or preventing viral infections. A particular method comprises administering to a subject in need thereof an effective amount of an adaptor associated kinase 1 inhibitor of the formula wherein R 1 , R 2 and R 3 are defined herein.
1. A method of treating or managing a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like coronavirus infection, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound, wherein the compound is (S)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine:
or a pharmaceutically acceptable salt thereof.
2. A method of treating or managing a CoV-229E-like coronavirus infection, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound, wherein the compound is (S)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine:
or a pharmaceutically acceptable salt thereof.
3. A method of treating or managing a CoV-OC43-like coronavirus infection, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound, wherein the compound is (S)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine:
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the subject displays one or more of fever, cough, shortness of breath, difficulty breathing, persistent pain in the chest, pressure in the chest, bluish lips or face, tiredness, runny nose, or sore throat.
5. The method of claim 1 , wherein the SARS-CoV-2-like coronavirus has at least 80, 90, 95, or 98 percent sequence identity with SEQ ID NO 1.
6. The method of claim 1 , wherein the compound is administered to the subject in a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier or excipient.
7. The method of claim 6 , wherein the pharmaceutical composition is in a pharmaceutical dosage form.
8. The method of claim 6 , wherein the administration is oral.
9. The method of claim 2 , wherein the subject displays one or more of fever, cough, shortness of breath, difficulty breathing, persistent pain in the chest, pressure in the chest, bluish lips or face, tiredness, runny nose, or sore throat.
10. The method of claim 2 , wherein the CoV-229E-like coronavirus has at least 80, 90, 95, or 98 percent sequence identity with SEQ ID NO 5.
11. The method of claim 2 , wherein the compound is administered to the subject in a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier or excipient.
12. The method of claim 11 , wherein the pharmaceutical composition is in a pharmaceutical dosage form.
13. The method of claim 11 , wherein the administration is oral.
14. The method of claim 3 , wherein the subject displays one or more of fever, cough, shortness of breath, difficulty breathing, persistent pain in the chest, pressure in the chest, bluish lips or face, tiredness, runny nose, or sore throat.
15. The method of claim 3 , wherein the CoV-OC43-like coronavirus has at least 80, 90, 95, or 98 percent sequence identity with SEQ ID NO 9.
16. The method of claim 3 , wherein the compound is administered to the subject in a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier or excipient.
17. The method of claim 16 , wherein the pharmaceutical composition is in a pharmaceutical dosage form.
18. The method of claim 16 , wherein the administration is oral.