Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV.
Identifieur interne : 002B60 ( PubMed/Corpus ); précédent : 002B59; suivant : 002B61Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV.
Auteurs : John T-A Hsu ; Chih-Jung Kuo ; Hsing-Pang Hsieh ; Yeau-Ching Wang ; Kuo-Kuei Huang ; Coney P-C Lin ; Ping-Fang Huang ; Xin Chen ; Po-Huang LiangSource :
- FEBS letters [ 0014-5793 ] ; 2004.
English descriptors
- KwdEn :
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Metals, Protease Inhibitors.
- chemical , pharmacology : Protease Inhibitors.
- chemical : Cysteine Endopeptidases, Endopeptidases.
- enzymology : SARS Virus.
- Amino Acid Sequence, Animals, Chlorocebus aethiops, Molecular Sequence Data, Vero Cells.
Abstract
3C-like (3CL) protease is essential for the life cycle of severe acute respiratory syndrome-coronavirus (SARS-CoV) and therefore represents a key anti-viral target. A compound library consisting of 960 commercially available drugs and biologically active substances was screened for inhibition of SARS-CoV 3CL protease. Potent inhibition was achieved using the mercury-containing compounds thimerosal and phenylmercuric acetate, as well as hexachlorophene. As well, 1-10 microM of each compound inhibited viral replication in Vero E6 cell culture. Detailed mechanism studies using a fluorescence-based protease assay demonstrated that the three compounds acted as competitive inhibitors (Ki=0.7, 2.4, and 13.7 microM for phenylmercuric acetate, thimerosal, and hexachlorophene, respectively). A panel of metal ions including Zn2+ and its conjugates were then evaluated for their anti-3CL protease activities. Inhibition was more pronounced using a zinc-conjugated compound (1-hydroxypyridine-2-thione zinc; Ki=0.17 microM) than using the ion alone (Ki=1.1 microM).
DOI: 10.1016/j.febslet.2004.08.015
PubMed: 15358550
Links to Exploration step
pubmed:15358550Le document en format XML
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uniqKey="Huang K" first="Kuo-Kuei" last="Huang">Kuo-Kuei Huang</name></author><author><name sortKey="Lin, Coney P C" sort="Lin, Coney P C" uniqKey="Lin C" first="Coney P-C" last="Lin">Coney P-C Lin</name></author><author><name sortKey="Huang, Ping Fang" sort="Huang, Ping Fang" uniqKey="Huang P" first="Ping-Fang" last="Huang">Ping-Fang Huang</name></author><author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name></author><author><name sortKey="Liang, Po Huang" sort="Liang, Po Huang" uniqKey="Liang P" first="Po-Huang" last="Liang">Po-Huang Liang</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2004">2004</date><idno type="RBID">pubmed:15358550</idno><idno type="pmid">15358550</idno><idno type="doi">10.1016/j.febslet.2004.08.015</idno><idno type="wicri:Area/PubMed/Corpus">002B60</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" 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Kuo Kuei" sort="Huang, Kuo Kuei" uniqKey="Huang K" first="Kuo-Kuei" last="Huang">Kuo-Kuei Huang</name></author><author><name sortKey="Lin, Coney P C" sort="Lin, Coney P C" uniqKey="Lin C" first="Coney P-C" last="Lin">Coney P-C Lin</name></author><author><name sortKey="Huang, Ping Fang" sort="Huang, Ping Fang" uniqKey="Huang P" first="Ping-Fang" last="Huang">Ping-Fang Huang</name></author><author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name></author><author><name sortKey="Liang, Po Huang" sort="Liang, Po Huang" uniqKey="Liang P" first="Po-Huang" last="Liang">Po-Huang Liang</name></author></analytic><series><title level="j">FEBS letters</title><idno type="ISSN">0014-5793</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Chlorocebus aethiops</term><term>Cysteine Endopeptidases</term><term>Endopeptidases</term><term>Metals (chemistry)</term><term>Molecular Sequence Data</term><term>Protease Inhibitors (chemistry)</term><term>Protease Inhibitors (pharmacology)</term><term>SARS Virus (enzymology)</term><term>Vero Cells</term><term>Viral Proteins (antagonists & inhibitors)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Metals</term><term>Protease Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Protease Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Chlorocebus aethiops</term><term>Molecular Sequence Data</term><term>Vero Cells</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">3C-like (3CL) protease is essential for the life cycle of severe acute respiratory syndrome-coronavirus (SARS-CoV) and therefore represents a key anti-viral target. A compound library consisting of 960 commercially available drugs and biologically active substances was screened for inhibition of SARS-CoV 3CL protease. Potent inhibition was achieved using the mercury-containing compounds thimerosal and phenylmercuric acetate, as well as hexachlorophene. As well, 1-10 microM of each compound inhibited viral replication in Vero E6 cell culture. Detailed mechanism studies using a fluorescence-based protease assay demonstrated that the three compounds acted as competitive inhibitors (Ki=0.7, 2.4, and 13.7 microM for phenylmercuric acetate, thimerosal, and hexachlorophene, respectively). A panel of metal ions including Zn2+ and its conjugates were then evaluated for their anti-3CL protease activities. Inhibition was more pronounced using a zinc-conjugated compound (1-hydroxypyridine-2-thione zinc; Ki=0.17 microM) than using the ion alone (Ki=1.1 microM).</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">15358550</PMID><DateCompleted><Year>2004</Year><Month>11</Month><Day>02</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>18</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0014-5793</ISSN><JournalIssue CitedMedium="Print"><Volume>574</Volume><Issue>1-3</Issue><PubDate><Year>2004</Year><Month>Sep</Month><Day>10</Day></PubDate></JournalIssue><Title>FEBS letters</Title><ISOAbbreviation>FEBS Lett.</ISOAbbreviation></Journal><ArticleTitle>Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV.</ArticleTitle><Pagination><MedlinePgn>116-20</MedlinePgn></Pagination><Abstract><AbstractText>3C-like (3CL) protease is essential for the life cycle of severe acute respiratory syndrome-coronavirus (SARS-CoV) and therefore represents a key anti-viral target. A compound library consisting of 960 commercially available drugs and biologically active substances was screened for inhibition of SARS-CoV 3CL protease. Potent inhibition was achieved using the mercury-containing compounds thimerosal and phenylmercuric acetate, as well as hexachlorophene. As well, 1-10 microM of each compound inhibited viral replication in Vero E6 cell culture. Detailed mechanism studies using a fluorescence-based protease assay demonstrated that the three compounds acted as competitive inhibitors (Ki=0.7, 2.4, and 13.7 microM for phenylmercuric acetate, thimerosal, and hexachlorophene, respectively). A panel of metal ions including Zn2+ and its conjugates were then evaluated for their anti-3CL protease activities. Inhibition was more pronounced using a zinc-conjugated compound (1-hydroxypyridine-2-thione zinc; Ki=0.17 microM) than using the ion alone (Ki=1.1 microM).</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hsu</LastName><ForeName>John T-A</ForeName><Initials>JT</Initials><AffiliationInfo><Affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, National Defense Medical Center, Taipei 115, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuo</LastName><ForeName>Chih-Jung</ForeName><Initials>CJ</Initials></Author><Author ValidYN="Y"><LastName>Hsieh</LastName><ForeName>Hsing-Pang</ForeName><Initials>HP</Initials></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Yeau-Ching</ForeName><Initials>YC</Initials></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Kuo-Kuei</ForeName><Initials>KK</Initials></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Coney P-C</ForeName><Initials>CP</Initials></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Ping-Fang</ForeName><Initials>PF</Initials></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Xin</ForeName><Initials>X</Initials></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>Po-Huang</ForeName><Initials>PH</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>FEBS Lett</MedlineTA><NlmUniqueID>0155157</NlmUniqueID><ISSNLinking>0014-5793</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008670">Metals</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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