Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe 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 (Mpro, also called 3CLpro) 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 Mpro 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 inhibitor of the SARS-CoV-2 Mpro The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.
CitationScience. 2020;368(6489):409‐412. doi:10.1126/science.abb3405
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
JournalScience (New York, N.Y.)
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy.
- Authors: Goyal B, Goyal D
- Issue date: 2020 Jun 8
- Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M<sup>pro</sup> enzyme through in silico approach.
- Authors: Gurung AB, Ali MA, Lee J, Farah MA, Al-Anazi KM
- Issue date: 2020 Aug 15
- In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus.
- Authors: Eleftheriou P, Amanatidou D, Petrou A, Geronikaki A
- Issue date: 2020 May 29
- Structural plasticity of SARS-CoV-2 3CL M<sup>pro</sup> active site cavity revealed by room temperature X-ray crystallography.
- Authors: Kneller DW, Phillips G, O'Neill HM, Jedrzejczak R, Stols L, Langan P, Joachimiak A, Coates L, Kovalevsky A
- Issue date: 2020 Jun 24
- Structure of M<sup>pro</sup> from SARS-CoV-2 and discovery of its inhibitors.
- Authors: Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H
- Issue date: 2020 Jun