Alain Chambovey
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Alain Chambovey has a total of 14 co-authors. Here are the top co-authors by number of shared publications:
- Aengus Mac Sweeney
Idorsia Pharmaceuticals Ltd. Translational Sciences Allschwil Switzerland
1 shared publication - Alexander Metz
Idorsia Pharmaceuticals Ltd. Translational Sciences Allschwil Switzerland
1 shared publication - Chia-Ying Huang
Swiss Light Source Paul Scherrer Institute Villigen Switzerland
1 shared publication Céline Potot
Idorsia Pharmaceuticals Ltd., 4123 Allschwil, Switzerland
1 shared publication- Daniel Ritz
Idorsia Pharmaceuticals Ltd. Translational Sciences Allschwil Switzerland
1 shared publication Deniz Eris
Swiss Light Source, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland
1 shared publication
Latest Publications
- Open Access
Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket
To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate binding pocket. Of 631 fragments soaked, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (2 hits) or at crystal packing interfaces (3 hits). Notably, two fragments with a pose sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. Our structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography. Synopsis: An X-ray crystallographic screen on SARS-CoV-2 3CL protease resulted in 29 fragment hits, including two isatin-based reversible covalent binders, and revealed a strong influence of the crystal form used for fragment soaking on the bound conformation of three additional reference fragments.
Open AccessFragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket
To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate binding pocket. Of 631 fragments soaked, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (2 hits) or at crystal packing interfaces (3 hits). Notably, two fragments with a pose sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. Our structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography. Synopsis: An X-ray crystallographic screen on SARS-CoV-2 3CL protease resulted in 29 fragment hits, including two isatin-based reversible covalent binders, and revealed a strong influence of the crystal form used for fragment soaking on the bound conformation of three additional reference fragments.