Anti-viral compositions containing PIKfyve inhibitors and use thereof
The present invention relates to compositions containing a PIKfyve inhibitor, preferably apilimod, APY0201 or YM-201636, most preferably apilimod, for use in treating or preventing viral infections, preferably Ebola or Marburg virus infections. It also relates to a pharmaceutical pack or kit comprising apillimod and at least one additional anti-viral agent.
1. A method for inhibiting an Ebola or Marburg viral infection in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a composition comprising an effective amount of apilimod, or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the apilimod is apilimod free base or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the mammalian subject is a human.
4. The method of claim 1 , further comprising administering to the mammalian subject at least one additional anti-viral agent, either in the same composition as the apilimod or a pharmaceutically acceptable salt thereof, or in a different composition.
5. The method of claim 4 , wherein the anti-viral agent comprises an antibody or a combination of antibodies.
6. The method of claim 4 , wherein the anti-viral agent comprises a small interfering RNA (siRNA) or a combination of siRNA molecules.
7. The method of claim 6 , wherein the siRNA or combination of siRNA molecules targets one or more Ebola virus proteins.
8. The method of claim 7 , wherein the siRNA or combination of siRNA molecules targets one or more Ebola virus proteins selected from the group consisting of the Zaire Ebola L polymerase, Zaire Ebola membrane-associated protein (VP24), and Zaire Ebola polymerase complex protein (VP35).
9. The method of claim 4 , wherein the anti-viral agent is an interferon.
10. The method of claim 3 , wherein the apilimod, or a pharmaceutically acceptable salt thereof is administered via an oral, intravenous, or subcutaneous route.
11. The method of claim 10 , wherein the administration of the apilimod, or a pharmaceutically acceptable salt thereof is once daily, twice daily, or continuous for a period of time.
12. The method of claim 10 , wherein the apilimod, or a pharmaceutically acceptable salt thereof is administered in an amount of 70 to 1000 mg/day.
13. The method of claim 2 , wherein the pharmaceutically acceptable salt is selected from a sulfate, citrate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, besylate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and pamoate.
14. The method of claim 13 , wherein the pharmaceutically acceptable salt is selected from the group consisting of a chloride, methanesulfonate, fumarate, lactate, maleate, pamoate, phosphate, and tartrate.
15. The method of claim 1 , wherein the pharmaceutically acceptable salt is apilimod dimesylate.
16. The method of claim 15 , wherein the amount of apilimod dimesylate is from 0.001 mg/kg to about 1000 mg/kg.