Method for treating herpes viruses

Abstract

The present invention relates to a method for selecting an anti-herpes viral compound and a method for selectively inhibiting herpesvrus in a human host in need of such treatment. The present invention relates to a method for selecting an anti-herpes viral compound and a method for selectively inhibiting herpesvrus in a human host in need of such treatment.

We claim:  
     
         1 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a wild type herpes virus,    b) measuring IC 50  of the same compound that inhibits a binding domain mutant herpes virus which is the same strain as the wild type herpes virus,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.    
     
     
         2 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a binding domain mutant herpes virus,    b) measuring IC 50  of the same compound that inhibits a wild type herpes virus which is the same strain as the mutant herpes virus,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step a is at least 3 times greater than the IC 50  of step b.    
     
     
         3 . The method of  claim 1  or  2  wherein the herpes virus is HSV-1, HSV-2, HCMV, VZV, EBV, or HHV-8.  
     
     
         4 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a wild type HSV-1,    b) measuring IC 50  of the same compound that inhibits a binding domain mutant HSV-1 which is the same strain as the wild type herpes virus,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.    
     
     
         5 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a binding domain mutant HSV-1,    b) measuring IC 50  of the same compound that inhibits a wild type herpes virus which is the same strain as the mutant HSV-1,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step a is at least 3 times greater than the IC 50  of step b.    
     
     
         6 . The method of  claim 4  or  5  wherein HSV-1 is HSV-1 KOS, HSV-1 F, HSV-1 DJL or HSV-1 Patton.  
     
     
         7 . The method of  claim 5  or  6  wherein the mutation of a wild type herpes virus to mutant herpes virus is at amino acid 823 from valine to alanine.  
     
     
         8 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a wild type HSV-2,    b) measuring IC 50  of the same compound that inhibits a binding domain mutant HSV-2 which is the same strain as the wild type herpes virus,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.    
     
     
         9 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a binding domain mutant HSV-2,    b) measuring IC 50  of the same compound that inhibits a wild type herpes virus which is the same strain as the mutant HSV-2,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step a is at least 3 times greater than the IC 50  of step b.    
     
     
         10 . The method of  claim 8  or  9  wherein HSV-2 is HSV-2 MS, HSV-2 35D, or HSV-2 186.  
     
     
         11 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a wild type HCMV,    b) measuring IC 50  of the same compound that inhibits a binding domain mutant HCMV which is the same strain as the wild type herpes virus,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.    
     
     
         12 . A method of selecting compounds that inhibit herpes viruses comprising: 
 a) measuring IC 50  of a compound of interest that inhibits a binding domain mutant HCMV,    b) measuring IC 50  of the same compound that inhibits a wild type herpes virus which is the same strain of the mutant HCMV,    c) comparing IC 50  of step a with IC 50  of step b; and    d) selecting the compound of interest wherein the IC 50  of step a is at least 3 times greater than the IC 50  of step b.    
     
     
         13 . The method of  claim 8  or  9  wherein HCMV is AD169.  
     
     
         14 . The methods of claims  1 ,  4 ,  8 , or  11  wherein IC 50  of step b is at least 5 times greater than the IC 50  of step a.  
     
     
         15 . The methods of claims  2 ,  5 ,  9 , or  12  wherein IC 50  of step a is at least 5 times greater than the IC 50  of step b.  
     
     
         16 . A method for selectively treating diseases caused by herpes viruses in a human host comprising administering a compound to a human in need of such treatment wherein said compound inhibits herpes viruses by interaction with the binding domain in the viral DNA polymerase.  
     
     
         17 . A method for selectively inhibiting herpes viruses in a human host comprising administering a compound to a human in need of such treatment wherein IC 50  of the compound that inhibits a binding domain mutant herpes virus is at lease 3 times greater than IC 50  of the compound that inhibits a wild type herpes virus which is the same strain as the mutant herpes virus.  
     
     
         18 . The method of  claim 17  wherein IC 50  of the compound that inhibits a binding domain mutant herpes virus is at lease 5 times greater than IC 50  of the compound that inhibits a wild type herpes virus which is the same strain as the mutant herpes viruse.  
     
     
         19 . The method of  claim 17  wherein herpes viruses is HSV-1, HSV-2, HCMV, VZV, EBV, or HHV-8.  
     
     
         20 . A compound for treating herpesviral infections in a human host wherein IC 50  of the compound that inhibits a binding domain mutant herpes virus is at lease 5 times greater than IC 50  of the compound that inhibits a wild type herpes virus which is the same strain as the mutant herpes virus.  
     
     
         21 . A compound for treating herpesviral infections in a human host wherein said compound inhibits the herpesvirus by interacting with the binding domain in the viral DNA polymerase.  
     
     
         22 . The herpesviral infection of  claim 20  or  21  which is HSV-1, HSV-2, HCMV, VZV, EBV, or HHV-8 infection.  
     
     
         23 . A compound for the inhibiting of herpesvirus DNA polymerases wherein passage of a wild type herpes virus in the presence of said compound results a change of the wild type HSV-1 polymerases at amino acid 823 from valine to alanine.  
     
     
         24 . A compound for inhibiting herpesvirus DNA polymerases wherein passage of a wild type herpes virus in the presence of said compound results in a change of the wild type HCMV polymerases at amino acid 823 from valine to alanine and at amino acid 824 from valine to leuline.  
     
     
         25 . A mutant herpesvirus DNA molecule having a nucleotide sequence selected from a group consisting of SEQ.ID.NO. 1; SEQ.ID.NO. 3; SEQ.ID.NO. 5; SEQ.ID.NO. 7; SEQ.ID.NO. 9; and SEQ.ID.NO. 11.  
     
     
         26 . A mutant herpesvirus polymerase amino acid molecule having an amino acid sequence selected from a group consisting of SEQ.ID.NO. 2; SEQ.ID.NO. 4; SEQ.ID.NO. 6; SEQ.ID.NO. 8; SEQ.ID.NO. 10 and SEQ.ID.NO. 12.