Abstract
Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology
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Cells, Cultured
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Chymases
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Crystallography, X-Ray
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Dipeptides / chemistry
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Drug Design
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Humans
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Isoxazoles / chemical synthesis
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Isoxazoles / chemistry
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Isoxazoles / pharmacology
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Kinetics
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Lactams / chemical synthesis
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Lactams / chemistry
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Lactams / pharmacology
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Models, Molecular
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Molecular Mimicry
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Peptides / chemistry*
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Serine Endopeptidases / chemistry
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Serine Endopeptidases / metabolism*
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Serine Proteinase Inhibitors / chemical synthesis*
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Serine Proteinase Inhibitors / chemistry
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Serine Proteinase Inhibitors / pharmacology
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Severe acute respiratory syndrome-related coronavirus / drug effects
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Severe acute respiratory syndrome-related coronavirus / enzymology*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antiviral Agents
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Dipeptides
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Isoxazoles
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Lactams
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Peptides
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Serine Proteinase Inhibitors
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Serine Endopeptidases
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Chymases