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US 7,894,996 B2Granted
Structure of the hepatitis C NS5A protein
AssigneeThe Rockefeller University
InventorsCharles Rice, Timothy Tellinghuisen, Joseph Marcotrigiano
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Abstract
The present invention provides a crystallized N-terminal domain of an NS5A protein of hepatitis C virus, methods of producing the same and methods of use thereof. The present invention also relates to structural elements of the N-terminal domain of hepatitis C virus NS5A protein, and methods of inhibiting hepatitis C virus infection, replication and/or pathogenesis, by interacting with the same.
Claims8
A method of identifying a Hepatitis C virus (HCV) inhibitor in an inhibitor screening assay comprising:
- (a) determining the three-dimensional structure of the N-terminal domain I-Δh of an NS5A protein crystal, wherein said NS5A N-terminal domain I-Δh protein comprises a protein with at least 90% identity to amino acids 36-199 of SEQ ID NO:
- 4 and wherein said crystal has space group P4122 with unit cell dimensions of a=b=55.28Å, c=312.30 Å and α,β,γ=90°,
- (b) selecting or designing a potential inhibitor by performing rational drug design with said three-dimensional structure determined in part (a) wherein said selecting or designing is performed in conjunction with computer modeling;
- (c) contacting said potential inhibitor with an N-terminal domain of an NS5A protein of hepatitis C virus;
- and
- (d) detecting an ability of said potential inhibitor for inhibiting infection or replication of a hepatitis C virus.
3 more elements
Dependencies are inferred from the claim text.