Pharmaceutical compositions for treating ebola virus disease

Abstract

The present invention provides compounds and pharmaceutical compositions adapted to reduce a load of an RNA virus by at least 50%, the virus causing a pathogenic disease in a mammalian subject, the compound adapted to inhibit the formation of S-adenosyl methionine (SAM) in the virus, the compound being a DOT1L inhibitor, wherein the compound has a molecular weight of less than 1000, and a therapeutic index (TI=LD50:ED50) greater than 30 in the mammalian subject.

1 . A method for reducing a load of an infectious RNA virus causing a hemorrhagic pathogenic disease in a mammalian subject, the method comprising administering to said subject a pharmaceutical composition comprising a DOT1L inhibitor compound, said compound adapted to reduce a load of said RNA virus by at least 50% in said mammalian subject, wherein said compound has a therapeutic index (TI=LD 50 :ED 50 ) greater than 30 in said mammalian subject against said infectious RNA virus. 
     
     
         2 . A method according to  claim 1 , wherein said DOT1L inhibitor compound has an IC80 of less than 1 micromolar. 
     
     
         3 . A method according to  claim 1 , wherein said DOT1L inhibitor compound has an ED50 of less than 1 micromolar. 
     
     
         4 . A method according to  claim 1 , wherein said infectious RNA virus is Ebola virus. 
     
     
         5 . A method according to  claim 4 , wherein said DOT1L inhibitor compound is EPZ5676. 
     
     
         6 . A method according to  claim 1 , wherein the pharmaceutical composition is provided in a dosage form selected from an injectable dosage form, infusible dosage form, inhalable dosage form, edible dosage form, slow release dosage form, oral dosage form or combinations thereof. 
     
     
         7 . A method according to  claim 1 , wherein said mammalian subject is human. 
     
     
         8 . A method according to  claim 1 , wherein said disease has a survival rate of less than 50%. 
     
     
         9 . A method according to  claim 1 , wherein said load is reduced by 80% or more in said mammalian subject. 
     
     
         10 . A method according to  claim 1 , wherein said DOT1L inhibitor compound is a drug for a first indication and said hemorrhagic pathogenic disease is a second indication. 
     
     
         11 . A method according to  claim 1 , wherein said administering step is performed by oral, parenteral, transdermal, intra-venous or intra-muscular administration. 
     
     
         12 . A method according to  claim 1 , wherein said pharmaceutical composition further comprises an SAHH inhibitor. 
     
     
         13 . A method according to  claim 12 , wherein said pharmaceutical composition comprises two SAHH inhibitors.