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Article: Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: Identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata

TitleDevelopment of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: Identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata
Authors
Issue Date2006
PublisherWalter de Gruyter GmbH & Co KG. The Journal's web site is located at http://www.degruyter.de/journals/bc
Citation
Biological Chemistry, 2006, v. 387 n. 8, p. 1063-1074 How to Cite?
AbstractSARS-coronavirus (SARS-CoV) encodes a main protease, 3CL pro, which plays an essential role in the viral life cycle and is currently the prime target for discovering new anti-coronavirus agents. In this article, we report our success in developing a novel red-shifted (RS) fluorescence-based assay for 3CL pro and its application for identifying small-molecule anti-SARS agents from marine organisms. We have synthesised and characterised the first generation of a red-shifted internally quenched fluorogenic substrate (RS-IQFS) for 3CL pro based on resonance energy transfer between the donor and acceptor pair CAL Fluor Red 610 and Black Hole Quencher-1 (K m and k cat values of 14 μM and 0.65 min -1). The RS-IQFS primary sequence was selected based on the results of our screening analysis of 3CL pro performed using a series of blue-shifted (BS)-IQFSs corresponding to the 3CL pro-mediated cleavage junctions of the SARS-CoV polyproteins. In contrast to BS-IQFSs, the RS-IQFS was not susceptible to fluorescence interference from coloured samples and allowed for successful screening of marine natural products and identification of a coumarin derivative, esculetin-4-carboxylic acid ethyl ester, a novel 3CL pro inhibitor (IC 50=46 μM) and anti-SARS agent (EC 50=112 μM; median toxic concentration >800 μM) from the tropical marine sponge Axinella corrugata. Copyright © by Walter de Gruyter.
Persistent Identifierhttp://hdl.handle.net/10722/157452
ISSN
2015 Impact Factor: 2.71
2015 SCImago Journal Rankings: 1.607
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHamill, Pen_US
dc.contributor.authorHudson, Den_US
dc.contributor.authorKao, RYen_US
dc.contributor.authorChow, Pen_US
dc.contributor.authorRaj, Men_US
dc.contributor.authorXu, Hen_US
dc.contributor.authorRicher, MJen_US
dc.contributor.authorJean, Fen_US
dc.date.accessioned2012-08-08T08:50:05Z-
dc.date.available2012-08-08T08:50:05Z-
dc.date.issued2006en_US
dc.identifier.citationBiological Chemistry, 2006, v. 387 n. 8, p. 1063-1074en_US
dc.identifier.issn1431-6730en_US
dc.identifier.urihttp://hdl.handle.net/10722/157452-
dc.description.abstractSARS-coronavirus (SARS-CoV) encodes a main protease, 3CL pro, which plays an essential role in the viral life cycle and is currently the prime target for discovering new anti-coronavirus agents. In this article, we report our success in developing a novel red-shifted (RS) fluorescence-based assay for 3CL pro and its application for identifying small-molecule anti-SARS agents from marine organisms. We have synthesised and characterised the first generation of a red-shifted internally quenched fluorogenic substrate (RS-IQFS) for 3CL pro based on resonance energy transfer between the donor and acceptor pair CAL Fluor Red 610 and Black Hole Quencher-1 (K m and k cat values of 14 μM and 0.65 min -1). The RS-IQFS primary sequence was selected based on the results of our screening analysis of 3CL pro performed using a series of blue-shifted (BS)-IQFSs corresponding to the 3CL pro-mediated cleavage junctions of the SARS-CoV polyproteins. In contrast to BS-IQFSs, the RS-IQFS was not susceptible to fluorescence interference from coloured samples and allowed for successful screening of marine natural products and identification of a coumarin derivative, esculetin-4-carboxylic acid ethyl ester, a novel 3CL pro inhibitor (IC 50=46 μM) and anti-SARS agent (EC 50=112 μM; median toxic concentration >800 μM) from the tropical marine sponge Axinella corrugata. Copyright © by Walter de Gruyter.en_US
dc.languageengen_US
dc.publisherWalter de Gruyter GmbH & Co KG. The Journal's web site is located at http://www.degruyter.de/journals/bcen_US
dc.relation.ispartofBiological Chemistryen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntiviral Agents - Chemistry - Pharmacologyen_US
dc.subject.meshCell Proliferation - Drug Effectsen_US
dc.subject.meshCercopithecus Aethiopsen_US
dc.subject.meshCysteine Endopeptidases - Chemistry - Isolation & Purificationen_US
dc.subject.meshDrug Evaluation, Preclinicalen_US
dc.subject.meshKineticsen_US
dc.subject.meshMolecular Structureen_US
dc.subject.meshPorifera - Chemistry - Classificationen_US
dc.subject.meshProtease Inhibitors - Chemistry - Classification - Pharmacologyen_US
dc.subject.meshSars Virus - Drug Effects - Enzymologyen_US
dc.subject.meshSensitivity And Specificityen_US
dc.subject.meshSpectrometry, Fluorescence - Methodsen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshUmbelliferones - Chemistry - Pharmacologyen_US
dc.subject.meshVero Cellsen_US
dc.subject.meshViral Proteins - Antagonists & Inhibitors - Chemistry - Isolation & Purificationen_US
dc.subject.meshVirus Replication - Drug Effects - Physiologyen_US
dc.titleDevelopment of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: Identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugataen_US
dc.typeArticleen_US
dc.identifier.emailKao, RY:rytkao@hkucc.hku.hken_US
dc.identifier.authorityKao, RY=rp00481en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1515/BC.2006.131en_US
dc.identifier.pmid16895476-
dc.identifier.scopuseid_2-s2.0-33746867596en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33746867596&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume387en_US
dc.identifier.issue8en_US
dc.identifier.spage1063en_US
dc.identifier.epage1074en_US
dc.identifier.eissn1437-4315-
dc.identifier.isiWOS:000240351400008-
dc.publisher.placeGermanyen_US
dc.identifier.scopusauthoridHamill, P=8639505100en_US
dc.identifier.scopusauthoridHudson, D=35578243400en_US
dc.identifier.scopusauthoridKao, RY=7101675499en_US
dc.identifier.scopusauthoridChow, P=49761157000en_US
dc.identifier.scopusauthoridRaj, M=36885532600en_US
dc.identifier.scopusauthoridXu, H=8618239900en_US
dc.identifier.scopusauthoridRicher, MJ=7003916060en_US
dc.identifier.scopusauthoridJean, F=7006191250en_US

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