Method, composition and kit for antigenic binding of norwalk-like viruses

Abstract

A method for detecting a Norwalk-Like Virus (NLV) in a biological sample, comprising the steps of: obtaining a biological sample suspected of containing a NLV; contacting the biological sample with at least one human histo-blood group antigen to allow formation of a complex of the NLV with the antigen; and detecting the antigen NLV complex. The antigen-NLV complex can be detected by contacting the NLV-antigen complex with a NLV antibody that binds at an epitope of the NLV, and detecting the NLV antibody. The invention also includes a method for identifying compounds, and the compounds, that can inhibit the binding between a Norwalk-Like Virus (NLV) and histo-blood group antigen. The method includes the steps of contacting the NLV target with a compound; subsequently contacting the NLV with a standard compound that is known to be bound at a determinant binding site of the NLV; and determining whether the binding of the standard compound is decreased in the presence of the test compound, the decrease in binding being an indication that the test compound inhibits the binding activity of the NLV with the standard compound. In preferred embodiments, the standard compound is a histo-blood group antigen.

1 .- 8 . (canceled)  
   
   
       9 . A method of identifying a first test compound that inhibits the binding activity of a NLV, the method comprising the steps of: 
 a) contacting a NLV target with the test compound selected from the group consisting of a protein, a polypeptide, an oligosaccharide, a natural compound, and poly- and monoclonal antibodies, and mixtures thereof;    b) contacting the NLV with the standard compound that is known to bind with a determinant binding site of the NLV; and    c) determining whether the binding of the standard compound is decreased in the presence of the test compound, the decrease in binding being an indication that the test compound inhibits the binding activity of the NLV with the standard compound.    
   
   
       10 . The method according to  claim 9  wherein two or more of the NLV targets are contacted independently.  
   
   
       11 .- 14 . (canceled)  
   
   
       15 . A pharmaceutical composition comprising at least one compound selected from the group consisting of a protein, peptide, oligosaccharide, natural compound, a functionally equivalent molecule, and mixtures thereof, which competitively inhibits the binding of a NLV with a native histo-blood group antigens of a human host, and optionally a pharmaceutically acceptable carrier.  
   
   
       16 . A medicament comprising: 
 a) at least one carbohydrate compound, selected from: 
 1) at least one carbohydrate selected from the group consisting of fucosyl α1→3/4 N-acetyl glycosyl globoside (F3AG), a stabilized, synthetic F3AG analogue, and mixtures thereof, in an amount that inhibits binding of NLV strain 207 to gastroepithelium of a non-secretor individual;  
 2) at least one carbohydrate selected from the group consisting of fucosyl α1→2 galactose globoside (F2G), a stabilized, synthetic F2G analogue, and mixtures thereof, in an amount that inhibits binding of NLV strain 387 to gastroepithelium of a secretor individual;  
 3) at least one carbohydrate selected from the group consisting of N-acetyl galactosyl α1→3 galactosyl globoside (AG3G), N-acetyl galactosyl α1→4 galactosyl globoside (AG4G), a stabilized, synthetic AG3G analogue, a stabilized, synthetic AG4G analogue, and mixtures thereof, in an amount that inhibits binding of NLV strain MOH to gastroepithelium of a secretor individual;  
 4) at least one carbohydrate selected from the group consisting of galactosyl α1→3 galactosyl globoside (G3G), galactosyl α1→4 galactosyl globoside (G4G), a stabilized, synthetic G3G analogue, a stabilized, synthetic G4G analogue, and mixtures thereof, in an amount that inhibits binding of NLV strain MOH to gastroepithelium of a secretor individual; and  
 5) mixtures thereof; and  
   b) a pharmaceutically acceptable diluent, carrier or excipient.    
   
   
       17 .- 18 . (canceled)  
   
   
       19 . The method according to  claim 9  wherein the NLV is selected from the group consisting of strain 387, strain MOH, strain NV, strain 207, strain 02-1419, and a mixture thereof.  
   
   
       20 . The method according to  claim 9  wherein the standard compound is a human histo-blood group antigen.  
   
   
       21 . The method according to  claim 19  wherein the standard compound is a human histo-blood group antigen.  
   
   
       22 . The pharmaceutical composition according to  claim 15  wherein the compound binds to the NLV.  
   
   
       23 . The pharmaceutical composition according to  claim 22 , comprising a plurality of the compounds.  
   
   
       24 . The pharmaceutical composition according to  claim 22 , wherein the compound is an oligosaccharide.  
   
   
       25 . The pharmaceutical composition according to  claim 22  wherein the compound binds to the NLV with the binding specificity of the antigenic determinant of the human histo-blood group antigen.  
   
   
       26 . The pharmaceutical composition according to  claim 25  wherein the compound comprises a structure selected from the group consisting of the Fuc-α1→2 structure of the human histo-blood group H antigen; the GalNAc-α1→3 structure of the human histo-blood group A antigen; the Gal-α1→3 structure of the human histo-blood group B antigen; the Fuc-α1→3/4 structure of the human histo-blood Le a  antigen; and the Fuc-α1→2 structure of the human histo-blood Lewis b (Le b ) antigen.  
   
   
       27 . The pharmaceutical composition according to  claim 26  comprising a plurality of the compounds.  
   
   
       28 . The pharmaceutical composition according to  claim 27  wherein the plurality of compounds comprise the structures of the Fuc-α1→2 structure of the human histo-blood group H antigen; the GalNAc-α1→3 structure of the human histo-blood group A antigen; the Gal-α1→3 structure of the human histo-blood group B antigen; the Fuc-α1→3/4 structure of the human histo-blood Le a  antigen; and the Fuc-α1→2 structure of the human histo-blood Lewis b (Le b ) antigen.  
   
   
       29 . The pharmaceutical composition according to  claim 27  wherein the plurality of compounds are oligosaccharides.  
   
   
       30 . The pharmaceutical composition according to  claim 28  wherein the plurality of compounds are oligosaccharides.  
   
   
       31 . The pharmaceutical composition according to  claim 22 , in the form of a dose comprising from about 100 to about 10,000 units.  
   
   
       32 . The pharmaceutical composition according to  claim 31  wherein the dose comprises from about 1,000 to about 10,000 units.  
   
   
       33 . The medicament according to  claim 16 , comprising a plurality of the carbohydrate compounds, comprising at least one each of compounds 1), 2), 3), and 4).