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PDBsum entry 6y2f
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Viral protein
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PDB id
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6y2f
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References listed in PDB file
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Key reference
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Title
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Crystal structure of sars-Cov-2 main protease provides a basis for design of improved α-Ketoamide inhibitors.
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Authors
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L.Zhang,
D.Lin,
X.Sun,
U.Curth,
C.Drosten,
L.Sauerhering,
S.Becker,
K.Rox,
R.Hilgenfeld.
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Ref.
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Science, 2020,
368,
409-412.
[DOI no: ]
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PubMed id
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Abstract
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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
(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.
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