noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication

We report the discovery and optimization of a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). This unique protease is not only responsible for processing the viral polyprotein into its functional units but is al...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 2008-10, Vol.105 (42), p.16119-16124
Hauptverfasser:	Ratia, Kiira, Pegan, Scott, Takayama, Jun, Sleeman, Katrina, Coughlin, Melissa, Baliji, Surendranath, Chaudhuri, Rima, Fu, Wentao, Prabhakar, Bellur S, Johnson, Michael E, Baker, Susan C, Ghosh, Arun K, Mesecar, Andrew D
Format:	Artikel
Sprache:	eng
Schlagworte:	60 APPLIED LIFE SCIENCES Active sites Antiviral Agents - chemistry Antiviral Agents - classification Antiviral Agents - metabolism Antiviral Agents - pharmacology Antivirals BASIC BIOLOGICAL SCIENCES Biochemistry Biological Sciences CATALYSIS Coronavirus Crystallography, X-Ray CYSTEINE Cysteine Endopeptidases - chemistry Cysteine Endopeptidases - metabolism Cytotoxicity Endopeptidases - chemistry Endopeptidases - metabolism ENZYME INHIBITORS Enzyme Inhibitors - chemistry Enzyme Inhibitors - classification Enzyme Inhibitors - metabolism Enzyme Inhibitors - pharmacology ENZYMES FUNCTIONALS HOST HUMAN POPULATIONS Hydrogen bonds Immune system INHIBITION Inhibitory concentration 50 Models, Molecular OPTIMIZATION Polyproteins PROCESSING Proteases Protein Binding Proteinase inhibitors Proteins RESPIRATORY SYSTEM DISEASES SARS virus SARS Virus - drug effects SARS Virus - physiology Severe acute respiratory syndrome SPECIFICITY Substrate Specificity TARGETS Ubiquitins UNITS Viral Proteins - antagonists & inhibitors Viral Proteins - chemistry Viral Proteins - metabolism Virus Replication - drug effects Viruses
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