Cloning, overexpression and therapeutic use of bioactive histidine ammonia lyase

Abstract

Histidine ammonia lyase (HAL) isolated from Corynebacteriaceae can decrease serum histidine levels, induce accumulation of urocanic acid, and is not inhibited by L-histidinol. As a result, histidine ammonia lyases similar to the one isolated from Corynebacteriaceae are uniquely suitable for combination therapy with L-histidinol to treat histidine- and/or histamine-dependent pathologies, for example, infectious viruses, such as human Respiratory Syncytial Virus (RSV), Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV), as well as cancers.

1 - 23 . (canceled)  
     
     
         24 . A method of treating or preventing a viral infection comprising administering a therapeutically effective amount of a composition comprising a histidine analog or a salt or ester thereof to a patient suffering from the viral infection.  
     
     
         25 . The method according to  claim 24 , wherein the histidine analog is selected from the group consisting of histidinol, histidinal, imidazole glycerol phosphate, imidazole acetol phosphate, and histidinol phosphate.  
     
     
         26 . The method according to  claim 24 , wherein the histidine analog comprises formula (I):  
       
         
           
           
               
               
           
         
       
       wherein each R is independently a 1-, 2- or 3- carbon alkyl, a 2- to 3-carbon alkene, or a 2- to 3-carbon alkyne; wherein each R independently is optionally substituted with one or more groups selected from the group consisting of —OH, —SH, and ═O; and wherein Y is a five- or six-membered heterocyclic ring, having one or more hetero atoms selected from the group consisting of N, S, and O.  
     
     
         27 . The method according to  claim 26 , wherein R is a 1-carbon alkyl.  
     
     
         28 . The method according to  claim 26 , wherein Y is a five-membered ring.  
     
     
         29 . The method according to  claim 28 , wherein Y is an imidazole moiety.  
     
     
         30 . The method according to  claim 24 , wherein the histidine analog comprises formula (II):  
       
         
           
           
               
               
           
         
       
     
     
         31 . The method according to  claim 30 , wherein the composition has a concentration of the histidine analog or the salt or ester greater than 0.5 mM.  
     
     
         32 . The method according to  claim 30 , wherein the composition has a concentration of the histidine analog or the salt or ester greater than 1.0 mM.  
     
     
         33 . The method according to  claim 30 , wherein the composition has a concentration of the histidine analog or the salt or ester greater than 1.5 mM.  
     
     
         34 . The method according to  claim 30 , wherein the composition has a concentration of the histidine analog or the salt or ester greater than 2.0 mM.  
     
     
         35 . The method according to  claim 30 , wherein the composition has a concentration of the histidine analog or the salt or ester greater than 2.5 mM.  
     
     
         36 . The method according to  claim 30 , wherein the composition has a concentration of the histidine analog or the salt or ester greater than 3.0 mM.  
     
     
         37 . The method according to  claim 26 , wherein the composition has a concentration of the histidine analog or the salt or ester greater than 3.0 mM.  
     
     
         38 . The method according to  claim 24 , wherein the viral infection comprises a DNA virus, an RNA virus, or a retrovirus.  
     
     
         39 . The method according to  claim 24 , wherein the viral infection is caused by Herpes Simplex Virus, Human Respiratory Syncytial Virus, or Human Immunodeficienty Virus.  
     
     
         40 . The method according to  claim 24 , wherein the patient is a human.  
     
     
         41 . The method according to  claim 24 , wherein the ester is selected from the group consisting of phosphoric acid esters and carboxylic acid esters.