HCV NS3-NS4 Protease Resistance Mutants

A polynucleotide that encodes a biologically active fragment of an HCV NS3/4A protease, the fragment of said polynucleotide is characterized in that it encodes an HCV NS3/4A protease domain that comprises a codon that corresponds to codon 156 of the wild-type polynucleotide and/or the codon that corresponds to codon 168 of the wild-type polynucleotide, wherein said codon that corresponds to codon 156 and/or said codon that corresponds to codon 168 is mutated such that it does not encode an alanine at 156 and/or aspartic acid at 168.

An isolated HCV NS3/4A protease protein or biologically active fragment or biologically active analog thereof comprising a sequence in which the amino acid residue which corresponds to amino acid 156 of wild-type HCV NS3/4A protease is not an alanine residue and/or amino acid residue which corresponds to amino acid 168 HCV NS3/4A protease is not an aspartic acid residue.

A method for determining whether an HCV infection in a patient is drug-resistant comprising:

• a) collecting a biological sample from the HCV infected patient;
• and
• b) evaluating whether the plasma sample contains nucleic acid encoding a mutant HCV NS3/4A protease, wherein the presence of said mutant HCV NS3/4A protease is indicative of said patient having a drug-resistant HCV infection.

A method for evaluating whether a HCV-infected patient has a decreased sensitivity or susceptibility to VX-950 comprising evaluating whether said patient has a Hepatitis C virus NS3/4A protease DNA having a mutation at the codon that encodes residue 156 of wild-type Hepatitis C virus NS3/4A protease.

A method for evaluating whether a HCV-infected patient has a decreased sensitivity or susceptibility to a protease inhibitor comprising evaluating whether said patient has a Hepatitis C virus NS3/4A protease DNA having a mutation at the codon that encodes residue 156 of wild-type Hepatitis C virus NS3/4A protease.