PDBsum entry 6y2f

Viral protein

PDB id: 6y2f

Contents

Protein chain

303 a.a.

Ligands

DMS

O6K

Waters ×177

PDB id:

6y2f

Name:

Viral protein

Title:

Crystal structure (monoclinic form) of the complex resulting from the reaction between sars-cov-2 (2019-ncov) main protease and tert-butyl (1-((s)-1-(((s)-4-(benzylamino)-3,4-dioxo-1-((s)-2-oxopyrrolidin-3- yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2- dihydropyridin-3-yl)carbamate (alpha-ketoamide 13b)

Structure:

3c-like proteinase. Chain: a. Synonym: 3cl-pro,3clp,main protease,mpro,non-structural protein 5, nsp5,sars coronavirus main proteinase. Engineered: yes

Source:

Severe acute respiratory syndrome coronavirus 2. Organism_taxid: 2697049. Gene: rep, 1a-1b. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.95Å R-factor: 0.178 R-free: 0.219

Authors:

L.Zhang,D.Lin,X.Sun,R.Hilgenfeld

Key ref:

L.Zhang et al. (2020). Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 368, 409-412. PubMed id: 32198291 DOI: 10.1126/science.abb3405

Date:

15-Feb-20 Release date: 04-Mar-20

Protein chain

P0DTD1  (R1AB_SARS2) -

Enzyme reactions

• Enzyme class: E.C.3.4.22.69 - Sars coronavirus main proteinase.

DOI no: 10.1126/science.abb3405

Science 368:409-412 (2020)

PubMed id: 32198291

Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors.

L.Zhang, D.Lin, X.Sun, U.Curth, C.Drosten, L.Sauerhering, S.Becker, K.Rox, R.Hilgenfeld.

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 inhibitor of the SARS-CoV-2 M^pro The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.