Development of influenza A antivirals
View Patent ↗The present invention includes compositions, methods and systems to isolate and characterize novel antiviral agents by contacting the antiviral agent with the F2F3 zinc fingers of a CPSF30 protein and an Influenza A NS1A protein; and determining whether the binding between the CPSF30 protein and the Influenza A NS1A protein is reduced.
1. A method for identifying a candidate antiviral agent comprising:
providing a candidate antiviral agent;
mixing the candidate antiviral agent with a solution comprising an F2F3 zinc finger portion of an CPSF30 protein and an Influenza A NS1A protein; and
determining whether the candidate antiviral agent inhibits the binding between the F2F3 zinc fingers portion of an CPSF30 protein and the Influenza A NS1A protein, wherein an inhibition of binding identifies a candidate antiviral agent.
2. The method of claim 1 , wherein the step of determining the binding between F2F3 zinc fingers and Influenza A NS1A protein is performed by determining the production of interferon-α/β (IFN-α/β) antiviral mRNAs by the Influenza A.
3. The method of claim 1 , wherein the step of determining whether the binding agents inhibits binding in vitro.
4. The method of claim 1 , wherein the step of determining whether the binding agents inhibits binding in vitro is adapted for high throughput detection.
5. The method of claim 1 , wherein the step of determining the binding occurs within a cell.
6. The method of claim 1 , wherein the Influenza A is any mammalian Influenza A virus.
7. The method of claim 1 , wherein the Influenza A is any mammalian Influenza A virus strain selected from H3N2, H1N1, H2N2, H7N7 and H5N1 (avian influenza virus).
8. The method of claim 1 , wherein agent is selected from a compound library.
9. The method of claim 1 , wherein agent is provided to an animal suspected of having a viral infection in a pharmaceutically effective amount.
10. The method of claim 1 , wherein agent is isolated from a compound library.
11. A method for identifying a candidate antiviral agent from a pool of test compounds comprising:
Providing a pool of test compounds that may contain a candidate antiviral agent;
contacting the pool of test compounds with one or more F2F3 zinc fingers of a CPSF30 protein and an Influenza A NS1A protein;
measuring whether the binding between the F2F3 zinc fingers and the Influenza A NS1A protein is reduced; and
isolating a candidate antiviral agent from the pool of test compounds;
wherein reduction of binding between the F2F3 zinc fingers and the Influenza A NS1A protein in the presence of the candidate antiviral agent identifies said candidate antiviral agent.
12. The method of claim 11 , further comprising measuring the ability of the candidate agent to inhibit Influenza A virus replication.
13. The method of claim 11 , wherein the Influenza A is any mammalian Influenza A virus strain selected from H3N2, H1N1, H2N2, H7N7 and H5N1 (avian influenza virus).
14. The method of claim 11 , wherein the step of determining the binding between F2F3 zinc fingers of CPSF30 and Influenza A NS1A protein is the production of interferon-α/β (IFN-α/β) antiviral mRNAs by the Influenza A.
15. The method of claim 11 , wherein the step of determining whether the binding agents inhibits binding in vitro.
16. The method of claim 11 , wherein the step of determining whether the binding agents inhibit binding in vitro is adapted for high throughput detection.
17. The method of claim 11 , wherein the step of determining the binding is in a cell.
18. A method for identifying an antiviral agent for a human comprising the steps of:
selecting the antiviral agent based on its ability to prevent the interaction between one or more F2F3 zinc fingers of an CPSF30 protein and an Influenza A NS1A protein; and
selecting the antiviral agent that has antiviral activity without an adverse effect on the human cell.
19. The method of claim 18 , wherein the step of selecting an agent is conducted in vitro.
20. The method of claim 18 , wherein the step of selecting an agent is adapted for high throughput detection.
21. The method of claim 18 , wherein the Influenza A is any mammalian Influenza A virus.
22. The method of claim 18 , wherein the Influenza A is any mammalian Influenza A virus strain selected from H3N2, H1N1, H2N2, H7N7 and H5N1 (avian influenza virus).
23. A method for identifying a candidate antiviral agent comprising:
mixing the candidate antiviral agent with a solution comprising an F2F3 zinc finger portion of an CPSF30 protein and an Influenza A NS1A protein; and
determining whether the candidate antiviral agent inhibits the binding between the F2F3 zinc fingers portion of an CPSF30 protein and the Influenza A NS1A protein, wherein a detectable marker is attached on one or both the F2F3 zinc fingers and the Influenza A NS1A protein and an inhibition of binding identifies a candidate antiviral agent.
24. A method for identifying a candidate antiviral agent from a pool of test compounds comprising:
Providing a pool of test compounds that may contain a candidate antiviral agent;
contacting the pool of test compounds with one or more F2F3 zinc fingers of an CPSF30 protein and an Influenza A NS1A protein, wherein a detectable marker is on one or bother the F2F3 zinc fingers and the Influenza A NS1A protein;
measuring whether the binding between the F2F3 zinc fingers and the Influenza A NS1A protein is reduced;
isolating a candidate antiviral agent from the pool of test compounds;
wherein reduction of binding between the F2F3 zinc fingers and the Influenza A NS1A protein in the presence of the candidate antiviral agent identifies said candidate antiviral agent.