Premium
Inside Cover: Induced‐Fit Binding of the Macrocyclic Noncovalent Inhibitor TMC435 to its HCV NS3/NS4A Protease Target (Angew. Chem. Int. Ed. 9/2010)
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 - Reports
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201000389
Subject(s) - protease , hepatitis c virus , ns3 , protease inhibitor (pharmacology) , virology , chemistry , cover (algebra) , enzyme , virus , biochemistry , biology , engineering , viral load , antiretroviral therapy , mechanical engineering
The anti‐HCV activity of TMC435, currently in phase 2b clinical studies as an HCV therapeutic (HCV=hepatitis C virus), is based on inhibition of the NS3/4A protease of the virus. As M. D. Cummings and co‐workers describe in their Communication on page 1652 ff., binding of TMC435 to the target enzyme involves an induced fit, leading to occupancy of an extended S2 subsite. The authors thank J. M. Berke, E. Fransen, and L. Geeraert for assisting with the graphics.