About: Synergistic Inhibitor Binding to the Papain-Like Protease of Human SARS Coronavirus – Mechanistic and Inhibitor Design Implications

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About: Synergistic Inhibitor Binding to the Papain-Like Protease of Human SARS Coronavirus – Mechanistic and Inhibitor Design Implications Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Synergistic Inhibitor Binding to the Papain-Like Protease of Human SARS Coronavirus – Mechanistic and Inhibitor Design Implications
Creator	Lee, Hyun Patel, Kavankumar Truong, Lena Johnson, Michael Cao, Shuyi Gatuz, Joseph Ghosh, Arun Hevener, Kirk
Source	Medline; PMC
abstract	We have previously developed two potent chemical classes that inhibit the essential papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, we applied a novel approach to identify small fragments that act synergistically with these inhibitors. A fragment library was screened in combination with four previously developed lead inhibitors by fluorescence-based enzymatic assays. Several fragment compounds synergistically enhanced the inhibitory activity of the lead inhibitors by approximately an order of magnitude. Surface plasmon resonance (SPR) measurements showed that three fragments bind specifically to the PLpro enzyme. Mode of inhibition, computational solvent mapping, and molecular docking studies suggest that these fragments bind adjacent to the binding site of the lead inhibitors and further stabilize the inhibitor-bound state. We propose potential next generation compounds based upon a computational, fragment-merging approach. This approach provides an alternative strategy for lead optimization in cases where direct co-crystallization is difficult.
has issue date	2013-06-20(xsd:dateTime)
bibo:doi	10.1002/cmdc.201300134
bibo:pmid	23788528
has license	bronze-oa
sha1sum (hex)	4728b8de2f3d9a4edfb7e08bdca292a658eb79e8
schema:url	https://doi.org/10.1002/cmdc.201300134
resource representing a document's title	Synergistic Inhibitor Binding to the Papain-Like Protease of Human SARS Coronavirus – Mechanistic and Inhibitor Design Implications
has PubMed Central identifier	PMC3954986
has PubMed identifier	23788528
schema:publication	ChemMedChem
resource representing a document's body	covid:4728b8de2f3d9a4edfb7e08bdca292a658eb79e8#body_text
is schema:about of	named entity 'measurements' named entity 'bind' named entity 'Protease' named entity 'DESIGN' named entity 'CLASSES' named entity 'CASES' named entity 'ADJACENT TO' named entity 'STABILIZE' named entity 'DIRECT' named entity 'PROVIDES' named entity 'DIFFICULT' named entity 'BINDING SITE' named entity 'POTENTIAL' named entity 'BASED' named entity 'MEASUREMENTS' named entity 'PREVIOUSLY' named entity 'GENERATION' named entity 'PAPAIN' named entity 'STUDY' named entity 'ACT' named entity 'COMBINATION' named entity 'SMALL' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'COMPUTATIONAL' named entity 'SUGGEST' named entity 'LEAD' named entity 'FRAGMENTS' named entity 'THESE' named entity 'NOVEL' named entity 'ALTERNATIVE' named entity 'ORDER' named entity 'HUMAN' named entity 'SARS CORONAVIRUS' named entity 'BIND' named entity 'MERGING' named entity 'FRAGMENT' named entity 'STATE' named entity 'ENZYME' named entity 'SITE OF' named entity 'BOUND' named entity 'HAVE' named entity 'ESSENTIAL' named entity 'APPLIED' named entity 'INHIBITOR' named entity 'SYNERGISTIC' named entity 'INHIBITORS' named entity 'ENHANCED' named entity 'MOLECULAR DOCKING' named entity 'INHIBITOR' named entity 'PROTEASE' named entity 'PAPAIN' named entity 'MODE' named entity 'FLUORESCENCE' named entity 'APPROACH' named entity 'INHIBITORY ACTIVITY' named entity 'FRAGMENT LIBRARY' named entity 'WHERE' named entity 'TO IDENTIFY' named entity 'MAPPING' named entity 'ENZYMATIC' named entity 'CO-CRYSTALLIZATION' named entity 'APPROXIMATELY' named entity 'BINDING' named entity 'LIKE' named entity 'INHIBITION' named entity 'STRATEGY' named entity 'MAGNITUDE' named entity 'SURFACE PLASMON RESONANCE' named entity 'PROTEASE' named entity 'LEAD OPTIMIZATION' named entity 'CHEMICAL' named entity 'STUDIES' named entity 'LIKE' named entity 'SOLVENT'

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