Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
German Center for Infection Research · University of Lübeck · +6 more institutions
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (M pro , also called 3CL pro ) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 M pro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, we developed the lead compound into a potent…
Citation impact
- FWCI
- 419.78
- Percentile
- 100%
- References
- 43
Authors
9- LZLinlin Zhang
German Center for Infection Research, University of Lübeck
- DLDaizong Lin
Changchun Discovery Sciences (China), University of Lübeck
- XSXinyuanyuan Sun
German Center for Infection Research, University of Lübeck
- UCUte Curth
Medizinische Hochschule Hannover
- CDChristian Drosten
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin
Topics & keywords
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
- Protease
- Coronavirus disease 2019 (COVID-19)
- 2019-20 coronavirus outbreak
- Basis (linear algebra)
- Chemistry
- Computational biology
- Virology
- Responsible consumption and production