Compounds and methods for diagnosis and treatment of viral infections
Compositions and methods of using these compositions that can include a targeting moiety and a therapeutic agent are described herein. These compositions can be used for diagnosing and/or treating flaviviridae—family viruses including Zika virus, dengue virus, and yellow fever.
1. A method of treating a disease caused by infection by a flaviviridae family virus comprising administering to a subject in need thereof an effective amount of a compound of Formula (II):
wherein each X is independently H, L1-A, or L2-R; each L1 and L2 are independently linkers;
each A independently comprises a therapeutic agent or a detection label or H;
each R independently comprises a CD206 targeting moiety or H; and
n is an integer greater than zero;
wherein at least one R is a CD206 targeting moiety and at least one A is a chemotherapeutic agent.
2. The method of claim 1 , wherein a linker is used to attach the one or more CD206 targeting moieties and/or one or more chemotherapeutic agent.
3. The method of claim 1 , wherein at least one L1 comprises a degradable linker.
4. The method of claim 1 , wherein at least one L1 comprises a hydrolysable linker.
5. The method of claim 1 , wherein at least one L1 comprises an acid-sensitive linker.
6. The method of claim 1 , wherein at least one L1 is a C2-12 hydrocarbon chain optionally interrupted by up to three heteroatoms selected from the group consisting of O, S and N.
7. The method of claim 1 , wherein at least one L1 comprises —(CH 2 )pS(CH 2 )qNH-, wherein p and q are integers from 0 to 5.
8. The method of claim 1 , wherein at least one L2 is a C 2 -12 hydrocarbon chain optionally interrupted by up to three heteroatoms selected from the group consisting of O, S and N.
9. The method of claim 1 , wherein at least one L2 comprises —(CH 2 )pS(CH 2 )qNH-, wherein p and q independently are integers from 0 to 5.
10. The method of claim 1 , wherein treatment is effective through binding of the compound to the CD206 expressing cells of the subject and not through binding to the virus.
11. The method of claim 1 , wherein administration of the compound treats the disease and decreases disease causing virus through binding of the subject's CD206 expressing cells.
12. A method of targeting a flaviviridae family virus by targeting macrophages comprising administering to a subject in need thereof an effective amount of a compound of Formula (II):
wherein each X is independently H, L1-A, or L2-R;
each L1 and L2 are independently linkers;
each A independently comprises a therapeutic agent or a detection label or H;
each R independently comprises a CD206 targeting moiety or H; and
n is an integer greater than zero;
wherein at least one R is a CD206 targeting moiety and at least one A is a chemotherapeutic agent to treat the disease and decrease the amount of disease-causing virus.
13. The method of claim 12 , wherein administration of the compound treats the disease and decreases disease causing virus through binding of the subject's CD206 expressing cells.
14. The method of claim 12 , wherein the chemotherapeutic agent is selected from the group consisting of a cytostatic agent, an alkylating agent, an antimetabolite agent, an anti-proliferative agent, a tubulin binding agent, an anthracycline drug that is not doxorubicin, a vinca drug, a podophyllotoxin drug, a toxic enzyme drug, a radiosensitizing drug, and a combination thereof.
15. A method of treating a disease caused by infection by a flaviviridae family virus comprising administering to a subject in need thereof an effective amount of compound comprising a dextran backbone having one or more CD206 targeting moieties and one or more chemotherapeutic agents attached thereto.
16. The method of claim 15 , wherein treatment is effective through binding of the compound to the CD206 expressing cells of the subject and not through binding to the virus.
17. The method of claim 15 , wherein administration of the compound treats the disease and decreases disease causing virus through binding of the subject's CD206 expressing cells.
18. The method of claim 15 , wherein a linker is used to attach the one or more CD206 targeting moieties and/or one or more chemotherapeutic agent.
19. The method of claim 18 , wherein the linker comprises a degradable linker.
20. The method of claim 18 , wherein the linker comprises a hydrolysable linker.