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Induced‐Fit Binding of the Macrocyclic Noncovalent Inhibitor TMC435 to its HCV NS3/NS4A Protease Target
Author(s) -
Cummings Maxwell D.,
Lindberg Jimmy,
Lin TseI,
de Kock Herman,
Lenz Oliver,
Lilja Elisabet,
Felländer Sara,
Baraznenok Vera,
Nyström Susanne,
Nilsson Magnus,
Vrang Lotta,
Edlund Michael,
Rosenquist Åsa,
Samuelsson Bertil,
Raboisson Pierre,
Simmen Kenneth
Publication year - 2010
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200906696
Subject(s) - ns3 , protease , protease inhibitor (pharmacology) , hepatitis c virus , chemistry , non covalent interactions , virology , computational biology , virus , biochemistry , biology , molecule , enzyme , hydrogen bond , organic chemistry , antiretroviral therapy , viral load
If the shoe fits : TMC435, a noncovalent small‐molecule inhibitor of the hepatitis C virus (HCV) NS3/NS4A protease, is currently undergoing clinical evaluation as an HCV therapeutic. In the crystal structure of the noncovalent NS3/NS4A protease–TMC435 complex the bound inhibitor exploits induced‐fit binding. The new structure is consistent with the emerging view of viral resistance to NS3/NS4A protease inhibitors.