ChloroquineV1, Pmc, Corpus, bibRecord, 000367

High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

Identifieur interne : 000367 ( Pmc/Corpus ); précédent : 000366; suivant : 000368

High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

Auteurs : Liang Shen ; Junwei Niu ; Chunhua Wang ; Baoying Huang ; Wenling Wang ; Na Zhu ; Yao Deng ; Huijuan Wang ; Fei Ye ; Shan Cen ; Wenjie Tan

Source :

Journal of Virology [ 0022-538X ] ; 2019.

RBID : PMC:6613765

Abstract

Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613765

DOI: 10.1128/JVI.00023-19
PubMed: 30918074
PubMed Central: 6613765

Links to Exploration step

PMC:6613765

Le document en format XML

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<author><name sortKey="Shen, Liang" sort="Shen, Liang" uniqKey="Shen L" first="Liang" last="Shen">Liang Shen</name>
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<author><name sortKey="Niu, Junwei" sort="Niu, Junwei" uniqKey="Niu J" first="Junwei" last="Niu">Junwei Niu</name>
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<author><name sortKey="Wang, Chunhua" sort="Wang, Chunhua" uniqKey="Wang C" first="Chunhua" last="Wang">Chunhua Wang</name>
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<author><name sortKey="Huang, Baoying" sort="Huang, Baoying" uniqKey="Huang B" first="Baoying" last="Huang">Baoying Huang</name>
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<author><name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name>
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<author><name sortKey="Cen, Shan" sort="Cen, Shan" uniqKey="Cen S" first="Shan" last="Cen">Shan Cen</name>
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<author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
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<author><name sortKey="Niu, Junwei" sort="Niu, Junwei" uniqKey="Niu J" first="Junwei" last="Niu">Junwei Niu</name>
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</nlm:aff>
</affiliation>
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<author><name sortKey="Wang, Chunhua" sort="Wang, Chunhua" uniqKey="Wang C" first="Chunhua" last="Wang">Chunhua Wang</name>
<affiliation><nlm:aff id="aff2"><addr-line>National Institutes for Food and Drug Control, Beijing, China</addr-line>
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<author><name sortKey="Huang, Baoying" sort="Huang, Baoying" uniqKey="Huang B" first="Baoying" last="Huang">Baoying Huang</name>
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<author><name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name>
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</nlm:aff>
</affiliation>
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<author><name sortKey="Zhu, Na" sort="Zhu, Na" uniqKey="Zhu N" first="Na" last="Zhu">Na Zhu</name>
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<author><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name>
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</nlm:aff>
</affiliation>
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<author><name sortKey="Wang, Huijuan" sort="Wang, Huijuan" uniqKey="Wang H" first="Huijuan" last="Wang">Huijuan Wang</name>
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</nlm:aff>
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<author><name sortKey="Ye, Fei" sort="Ye, Fei" uniqKey="Ye F" first="Fei" last="Ye">Fei Ye</name>
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<author><name sortKey="Cen, Shan" sort="Cen, Shan" uniqKey="Cen S" first="Shan" last="Cen">Shan Cen</name>
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<author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
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<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
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<imprint><date when="2019">2019</date>
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<front><div type="abstract" xml:lang="en"><p>Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs <italic>in vitro</italic>
. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Virol</journal-id>
<journal-id journal-id-type="hwp">jvi</journal-id>
<journal-id journal-id-type="pmc">jvi</journal-id>
<journal-id journal-id-type="publisher-id">JVI</journal-id>
<journal-title-group><journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">30918074</article-id>
<article-id pub-id-type="pmc">6613765</article-id>
<article-id pub-id-type="publisher-id">00023-19</article-id>
<article-id pub-id-type="doi">10.1128/JVI.00023-19</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject>
</subj-group>
</article-categories>
<title-group><article-title>High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses</article-title>
<alt-title alt-title-type="running-head">Broad-Spectrum Inhibitors of CoV Infection</alt-title>
<alt-title alt-title-type="short-authors">Shen et al.</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Shen</surname>
<given-names>Liang</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Niu</surname>
<given-names>Junwei</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Wang</surname>
<given-names>Chunhua</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Huang</surname>
<given-names>Baoying</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Wang</surname>
<given-names>Wenling</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Zhu</surname>
<given-names>Na</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Deng</surname>
<given-names>Yao</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Wang</surname>
<given-names>Huijuan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Ye</surname>
<given-names>Fei</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Cen</surname>
<given-names>Shan</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes" equal-contrib="no"><name><surname>Tan</surname>
<given-names>Wenjie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
<addr-line>NHC Key Laboratory of Biosafety, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China</addr-line>
</aff>
<aff id="aff2"><label>b</label>
<addr-line>National Institutes for Food and Drug Control, Beijing, China</addr-line>
</aff>
<aff id="aff3"><label>c</label>
<addr-line>Department of Immunology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China</addr-line>
</aff>
</contrib-group>
<contrib-group><contrib contrib-type="editor"><name><surname>Gallagher</surname>
<given-names>Tom</given-names>
</name>
<role>Editor</role>
<aff>Loyola University Chicago</aff>
</contrib>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Wenjie Tan, <email>tanwj28@163.com</email>
.</corresp>
<fn fn-type="equal"><p>L.S. and J.N. contributed equally to this work.</p>
</fn>
<fn fn-type="other"><p><bold>Citation</bold>
 Shen L, Niu J, Wang C, Huang B, Wang W, Zhu N, Deng Y, Wang H, Ye F, Cen S, Tan W. 2019. High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses. J Virol 93:e00023-19. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.00023-19">https://doi.org/10.1128/JVI.00023-19</ext-link>
.</p>
</fn>
</author-notes>
<pub-date pub-type="epreprint"><day>27</day>
<month>3</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="epub"><day>29</day>
<month>5</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><day>15</day>
<month>6</month>
<year>2019</year>
</pub-date>
<volume>93</volume>
<issue>12</issue>
<elocation-id>e00023-19</elocation-id>
<history><date date-type="received"><day>7</day>
<month>1</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>17</day>
<month>3</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2019 American Society for Microbiology.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
<license license-type="asm" xlink:href="https://doi.org/10.1128/ASMCopyrightv2"><license-p><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/ASMCopyrightv2">All Rights Reserved</ext-link>
.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="JVI.00023-19.pdf"></self-uri>
<abstract abstract-type="precis"><p>Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs <italic>in vitro</italic>
. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.</p>
</abstract>
<abstract><title>ABSTRACT</title>
<p>Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing <italic>Renilla</italic>
 luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs <italic>in vitro</italic>
. We screened 56 hits from the HTS data and validated 36 compounds <italic>in vitro</italic>
 using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs <italic>in vitro</italic>
 at low-micromolar concentrations. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of <italic>in vivo</italic>
 real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection.</p>
<p><bold>IMPORTANCE</bold>
 Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs <italic>in vitro</italic>
. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.</p>
</abstract>
<kwd-group><title>KEYWORDS</title>
<kwd>Coronaviruses</kwd>
<kwd>bioluminescence imaging</kwd>
<kwd>broad-spectrum</kwd>
<kwd>high-throughput screening</kwd>
<kwd>inhibitor</kwd>
<kwd>mice</kwd>
</kwd-group>
<funding-group><award-group id="award1"><funding-source><institution-wrap><institution>Megaproject for Infectious Disease Research of China</institution>
</institution-wrap>
</funding-source>
<award-id>2016ZX10004001-003</award-id>
<principal-award-recipient><name><surname>Tan</surname>
<given-names>Wenjie</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award2"><funding-source><institution-wrap><institution>National Key Research and Development Program of China</institution>
</institution-wrap>
</funding-source>
<award-id>2016YFD0500300</award-id>
<principal-award-recipient><name><surname>Tan</surname>
<given-names>Wenjie</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award3"><funding-source><institution-wrap><institution>National Key Research and Development Program of China</institution>
</institution-wrap>
</funding-source>
<award-id>2016YFC1200200</award-id>
<principal-award-recipient><name><surname>Huang</surname>
<given-names>Baoying</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<counts><count count="1" count-type="supplementary-material"></count>
<fig-count count="6"></fig-count>
<table-count count="1"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="66"></ref-count>
<page-count count="15"></page-count>
<word-count count="9427"></word-count>
</counts>
<custom-meta-group><custom-meta><meta-name>cover-date</meta-name>
<meta-value>June 2019</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>

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High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

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