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Article: Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics

TitleIdentification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics
Authors
Issue Date2004
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/chembiol
Citation
Chemistry And Biology, 2004, v. 11 n. 9, p. 1293-1299 How to Cite?
AbstractThe severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (M pro), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC 50 of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV M pro, Hel, and viral entry, respectively, exhibited potent antiviral activity (EC 50 < 10 μM) and comparable inhibitory activities in target-specific in vitro assays.
Persistent Identifierhttp://hdl.handle.net/10722/68193
ISSN
2015 Impact Factor: 5.774
2015 SCImago Journal Rankings: 3.282
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKao, RYen_HK
dc.contributor.authorTsui, WHWen_HK
dc.contributor.authorLee, TSWen_HK
dc.contributor.authorTanner, JAen_HK
dc.contributor.authorWatt, RMen_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorChen, Gen_HK
dc.contributor.authorChen, Zen_HK
dc.contributor.authorZhang, Len_HK
dc.contributor.authorHe, Ten_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorTse, Hen_HK
dc.contributor.authorTo, APCen_HK
dc.contributor.authorNg, LWYen_HK
dc.contributor.authorWong, BCWen_HK
dc.contributor.authorTsoi, HWen_HK
dc.contributor.authorYang, Den_HK
dc.contributor.authorHo, DDen_HK
dc.contributor.authorYuen, KYen_HK
dc.date.accessioned2010-09-06T06:02:15Z-
dc.date.available2010-09-06T06:02:15Z-
dc.date.issued2004en_HK
dc.identifier.citationChemistry And Biology, 2004, v. 11 n. 9, p. 1293-1299en_HK
dc.identifier.issn1074-5521en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68193-
dc.description.abstractThe severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (M pro), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC 50 of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV M pro, Hel, and viral entry, respectively, exhibited potent antiviral activity (EC 50 < 10 μM) and comparable inhibitory activities in target-specific in vitro assays.en_HK
dc.languageengen_HK
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/chembiolen_HK
dc.relation.ispartofChemistry and Biologyen_HK
dc.subject.meshAntiviral Agents - Chemical Synthesis - Chemistry - Pharmacology-
dc.subject.meshCarboxypeptidases - Antagonists & Inhibitors - Metabolism-
dc.subject.meshSars Virus - Drug Effects - Growth & Development - Metabolism - Physiology-
dc.subject.meshViral Matrix Proteins - Antagonists & Inhibitors - Metabolism-
dc.subject.meshSevere Acute Respiratory Syndrome - Drug Therapy-
dc.titleIdentification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical geneticsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1074-5521&volume=V11&issue=9&spage=1293&epage=1299&date=2004&atitle=Identification+of+Novel+Small-Molecule+Inhibitors+of Severe+Acute+Respiratory+Syndrome-Associated+Coronavirus+by+Chemical Geneticsen_HK
dc.identifier.emailKao, RY:rytkao@hkucc.hku.hken_HK
dc.identifier.emailTanner, JA:jatanner@hku.hken_HK
dc.identifier.emailWatt, RM:rmwatt@hku.hken_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.emailChen, G:ghc@yangtze.hku.hken_HK
dc.identifier.emailChen, Z:zchenai@hkucc.hku.hken_HK
dc.identifier.emailTse, H:herman@graduate.hku.hken_HK
dc.identifier.emailTsoi, HW:hwtsoi@hkucc.hku.hken_HK
dc.identifier.emailYang, D:yangdan@hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityKao, RY=rp00481en_HK
dc.identifier.authorityTanner, JA=rp00495en_HK
dc.identifier.authorityWatt, RM=rp00043en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.identifier.authorityChen, G=rp00671en_HK
dc.identifier.authorityChen, Z=rp00243en_HK
dc.identifier.authorityTse, H=rp00519en_HK
dc.identifier.authorityTsoi, HW=rp00439en_HK
dc.identifier.authorityYang, D=rp00825en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.chembiol.2004.07.013en_HK
dc.identifier.pmid15380189-
dc.identifier.scopuseid_2-s2.0-4644343545en_HK
dc.identifier.hkuros95092en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-4644343545&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume11en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1293en_HK
dc.identifier.epage1299en_HK
dc.identifier.isiWOS:000224228900012-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKao, RY=7101675499en_HK
dc.identifier.scopusauthoridTsui, WHW=36124344600en_HK
dc.identifier.scopusauthoridLee, TSW=7501439333en_HK
dc.identifier.scopusauthoridTanner, JA=35513993000en_HK
dc.identifier.scopusauthoridWatt, RM=7102907536en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridHu, L=7401557295en_HK
dc.identifier.scopusauthoridChen, G=35253368600en_HK
dc.identifier.scopusauthoridChen, Z=35271180800en_HK
dc.identifier.scopusauthoridZhang, L=35274165900en_HK
dc.identifier.scopusauthoridHe, T=16935084000en_HK
dc.identifier.scopusauthoridChan, KH=7406034307en_HK
dc.identifier.scopusauthoridTse, H=7006070596en_HK
dc.identifier.scopusauthoridTo, APC=36828058300en_HK
dc.identifier.scopusauthoridNg, LWY=7201477846en_HK
dc.identifier.scopusauthoridWong, BCW=46561507100en_HK
dc.identifier.scopusauthoridTsoi, HW=6603822102en_HK
dc.identifier.scopusauthoridYang, D=7404800756en_HK
dc.identifier.scopusauthoridHo, DD=7402971998en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK

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