RNA virus inhibitor compounds and uses thereof
The present disclosure provides compounds and methods for inhibiting a virus infection, such as a Baltimore Group IV RNA virus infection. Aspects of the present disclosure also include methods of treating a Baltimore Group IV RNA virus infection in a subject. The present disclosure also provides pharmaceutical compositions related to the same.
1. A compound of formula II:
wherein:
R 6 is selected from —CH 3 and —CHF 2 ;
each R 7 is independently selected from —H, -D and —CH 3 , or together two R 7 and the carbon they are attached to form a cyclopropyl group; and
Z is selected from —CH 2 CH 2 CH 2 — and —C(CH 3 ) 2 —;
or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
2. The compound of claim 1 , wherein the compound is selected from the following structures:
3. A method of inhibiting a Baltimore Group IV RNA virus in a cell infected with a Baltimore Group IV RNA virus, the method comprising contacting the cell with a compound of claim 1 .
4. The method of claim 3 , wherein the Baltimore Group IV RNA virus is selected from picornavirus, norovirus, and coronavirus.
5. The method of claim 4 , wherein the Baltimore Group IV RNA virus is selected from enterovirus, rhinovirus, coxsackie virus, norovirus and coronavirus.
6. The method of claim 5 , wherein the Baltimore Group IV RNA virus is coronavirus.
7. The method of claim 6 , wherein the coronavirus is one that causes disease in mammals.
8. The method of claim 7 , wherein the coronavirus causes disease in companion animals or livestock.
9. The method of claim 8 , wherein the coronavirus is a feline coronavirus.
10. The method of claim 9 , wherein the coronavirus is feline infectious peritonitis.
11. The method of claim 7 , wherein the coronavirus is a human coronavirus.
12. The method of claim 11 , wherein the coronavirus is selected from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), Severe Acute Respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle Eastern Respiratory syndrome-related coronavirus (MERS-CoV).
13. A method of treating a Baltimore Group IV RNA virus infection in a mammal, the method comprising administering to the mammal an effective amount of a compound according to claim 1 .
14. The method of claim 13 , wherein the mammal is selected from a companion animal and livestock.
15. The method of claim 14 , wherein the mammal is a feline.
16. The method of claim 13 , wherein the mammal is a human.
17. The method of claim 13 , wherein the Baltimore Group IV RNA virus is selected enterovirus, rhinovirus, coxsackie virus, norovirus and coronavirus.
18. The method of claim 17 , wherein the Baltimore Group IV RNA virus is selected from norovirus, and coronavirus.
19. The method of claim 18 , wherein the Baltimore Group IV RNA virus is human norovirus.
20. The method of claim 18 , wherein the Baltimore Group IV RNA virus is a coronavirus that causes disease in mammals.
21. The method of claim 20 , wherein the coronavirus is a feline coronavirus.
22. The method of claim 21 , wherein the feline coronavirus is feline infectious peritonitis.
23. The method of claim 20 , wherein the coronavirus is a human coronavirus.
24. The method of claim 23 , wherein the human coronavirus is selected from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), Severe Acute Respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle Eastern Respiratory syndrome-related coronavirus (MERS-CoV).