Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*
Identifieur interne : 001109 ( Pmc/Curation ); précédent : 001108; suivant : 001110Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*
Auteurs : Nan Zhou ; Ting Pan ; Junsong Zhang ; Qianwen Li ; Xue Zhang ; Chuan Bai ; Feng Huang ; Tao Peng ; Jianhua Zhang ; Chao Liu ; Liang Tao ; Hui ZhangSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2016.
Abstract
Ebola virus infection can cause severe hemorrhagic fever with a high mortality in
humans. The outbreaks of Ebola viruses in 2014 represented the most serious
Ebola epidemics in history and greatly threatened public health worldwide. The
development of additional effective anti-Ebola therapeutic agents is therefore
quite urgent. In this study, via high throughput screening of Food and Drug
Administration-approved drugs, we identified that teicoplanin, a glycopeptide
antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses
into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on
transcription- and replication-competent virus-like particles, with an
IC50 as low as 330 n
Url:
DOI: 10.1074/jbc.M116.716100
PubMed: 26953343
PubMed Central: 4861487
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Nan Zhou<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Pharmacology, Zhongshan School of Medicine,</nlm:aff>
<wicri:noCountry code="subfield">Zhongshan School of Medicine</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late
Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory
Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome
Coronavirus (SARS-CoV)<xref ref-type="fn" rid="FN1">*</xref>
</title>
<author><name sortKey="Zhou, Nan" sort="Zhou, Nan" uniqKey="Zhou N" first="Nan" last="Zhou">Nan Zhou</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
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<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pan, Ting" sort="Pan, Ting" uniqKey="Pan T" first="Ting" last="Pan">Ting Pan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
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<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
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<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
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<author><name sortKey="Zhang, Junsong" sort="Zhang, Junsong" uniqKey="Zhang J" first="Junsong" last="Zhang">Junsong Zhang</name>
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<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
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<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
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<author><name sortKey="Li, Qianwen" sort="Li, Qianwen" uniqKey="Li Q" first="Qianwen" last="Li">Qianwen Li</name>
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</affiliation>
<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
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<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
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<author><name sortKey="Zhang, Xue" sort="Zhang, Xue" uniqKey="Zhang X" first="Xue" last="Zhang">Xue Zhang</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
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<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
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<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
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<author><name sortKey="Bai, Chuan" sort="Bai, Chuan" uniqKey="Bai C" first="Chuan" last="Bai">Chuan Bai</name>
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<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
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<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Huang, Feng" sort="Huang, Feng" uniqKey="Huang F" first="Feng" last="Huang">Feng Huang</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
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<author><name sortKey="Peng, Tao" sort="Peng, Tao" uniqKey="Peng T" first="Tao" last="Peng">Tao Peng</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
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<author><name sortKey="Zhang, Jianhua" sort="Zhang, Jianhua" uniqKey="Zhang J" first="Jianhua" last="Zhang">Jianhua Zhang</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Chao" sort="Liu, Chao" uniqKey="Liu C" first="Chao" last="Liu">Chao Liu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Tao, Liang" sort="Tao, Liang" uniqKey="Tao L" first="Liang" last="Tao">Liang Tao</name>
<affiliation><nlm:aff id="aff2">Department of Pharmacology, Zhongshan School of Medicine,</nlm:aff>
<wicri:noCountry code="subfield">Zhongshan School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Zhang, Hui" sort="Zhang, Hui" uniqKey="Zhang H" first="Hui" last="Zhang">Hui Zhang</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=", and" id="aff3">Key Laboratory of Tropical Disease Control of Ministry of Education</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</nlm:aff>
<wicri:noCountry code="subfield">Guangdong</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2016">2016</date>
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<front><div type="abstract" xml:lang="en"><p>Ebola virus infection can cause severe hemorrhagic fever with a high mortality in
humans. The outbreaks of Ebola viruses in 2014 represented the most serious
Ebola epidemics in history and greatly threatened public health worldwide. The
development of additional effective anti-Ebola therapeutic agents is therefore
quite urgent. In this study, via high throughput screening of Food and Drug
Administration-approved drugs, we identified that teicoplanin, a glycopeptide
antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses
into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on
transcription- and replication-competent virus-like particles, with an
IC<sub>50</sub>
as low as 330 n<sc>m</sc>
. Comparative analysis further
demonstrated that teicoplanin is able to block the entry of Middle East
respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS)
envelope pseudotyped viruses as well. Teicoplanin derivatives such as
dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola,
MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola
virus entry by specifically inhibiting the activity of cathepsin L, opening a
novel avenue for the development of additional glycopeptides as potential
inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has
routinely been used in the clinic with low toxicity, our work provides a
promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS
virus infection.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Biol Chem</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id>
<journal-id journal-id-type="hwp">jbc</journal-id>
<journal-id journal-id-type="pmc">jbc</journal-id>
<journal-id journal-id-type="publisher-id">JBC</journal-id>
<journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title>
</journal-title-group>
<issn pub-type="ppub">0021-9258</issn>
<issn pub-type="epub">1083-351X</issn>
<publisher><publisher-name>American Society for Biochemistry and Molecular
Biology</publisher-name>
<publisher-loc>11200 Rockville Pike, Suite 302, Rockville, MD 20852-3110,
U.S.A.</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26953343</article-id>
<article-id pub-id-type="pmc">4861487</article-id>
<article-id pub-id-type="publisher-id">M116.716100</article-id>
<article-id pub-id-type="doi">10.1074/jbc.M116.716100</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Microbiology</subject>
</subj-group>
</article-categories>
<title-group><article-title>Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late
Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory
Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome
Coronavirus (SARS-CoV)<xref ref-type="fn" rid="FN1">*</xref>
</article-title>
<alt-title alt-title-type="short">Glycopeptide Antibiotics Inhibit Virus
Entry</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zhou</surname>
<given-names>Nan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
<xref ref-type="author-notes" rid="FN2"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pan</surname>
<given-names>Ting</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
<xref ref-type="author-notes" rid="FN2"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Junsong</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Qianwen</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Xue</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bai</surname>
<given-names>Chuan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Huang</surname>
<given-names>Feng</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peng</surname>
<given-names>Tao</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>‖</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Jianhua</given-names>
</name>
<xref ref-type="aff" rid="aff6">**</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Chao</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tao</surname>
<given-names>Liang</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>‡‡</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Hui</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>2</sup>
</xref>
</contrib>
<aff id="aff1">From the<label>‡</label>
Institute of Human Virology,</aff>
<aff id="aff2"><label>‡‡</label>
Department of Pharmacology, Zhongshan School of Medicine,</aff>
<aff id="aff3"><label>§</label>
Key Laboratory of Tropical Disease Control of Ministry of Education, and</aff>
<aff id="aff4"><label>¶</label>
Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong,</aff>
<aff id="aff5">the<label>‖</label>
Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510182, Guangdong, and</aff>
<aff id="aff6">the<label>**</label>
CAS Key Laboratory for Pathogenic Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>2</label>
To whom correspondence should be addressed.
Tel.: <phone>86-20-87332588</phone>
; Fax: <fax>86-20-87332588</fax>
; E-mail:
<email>zhangh92@mail.sysu.edu.cn</email>
.</corresp>
<fn fn-type="equal" id="FN2"><label>1</label>
<p>Both authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>22</day>
<month>4</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="epub"><day>7</day>
<month>3</month>
<year>2016</year>
</pub-date>
<volume>291</volume>
<issue>17</issue>
<fpage>9218</fpage>
<lpage>9232</lpage>
<history><date date-type="received"><day>16</day>
<month>1</month>
<year>2016</year>
</date>
<date date-type="rev-recd"><day>3</day>
<month>3</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© 2016 by The American Society for Biochemistry and
Molecular Biology, Inc.</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>The American Society for Biochemistry and Molecular Biology,
Inc.</copyright-holder>
<license><license-p>This article is made available via the PMC Open Access Subset for
unrestricted re-use and analyses in any form or by any means with
acknowledgement of the original source. These permissions are granted for
the duration of the COVID-19 pandemic or until permissions are revoked in
writing. Upon expiration of these permissions, PMC is granted a perpetual
license to make this article available via PMC and Europe PMC, consistent
with existing copyright protections.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="zbc01716009218.pdf"></self-uri>
<abstract><p>Ebola virus infection can cause severe hemorrhagic fever with a high mortality in
humans. The outbreaks of Ebola viruses in 2014 represented the most serious
Ebola epidemics in history and greatly threatened public health worldwide. The
development of additional effective anti-Ebola therapeutic agents is therefore
quite urgent. In this study, via high throughput screening of Food and Drug
Administration-approved drugs, we identified that teicoplanin, a glycopeptide
antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses
into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on
transcription- and replication-competent virus-like particles, with an
IC<sub>50</sub>
as low as 330 n<sc>m</sc>
. Comparative analysis further
demonstrated that teicoplanin is able to block the entry of Middle East
respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS)
envelope pseudotyped viruses as well. Teicoplanin derivatives such as
dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola,
MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola
virus entry by specifically inhibiting the activity of cathepsin L, opening a
novel avenue for the development of additional glycopeptides as potential
inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has
routinely been used in the clinic with low toxicity, our work provides a
promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS
virus infection.</p>
</abstract>
<kwd-group><kwd>antibiotics</kwd>
<kwd>Ebola virus</kwd>
<kwd>glycoprotein</kwd>
<kwd>lysosome</kwd>
<kwd>virus entry</kwd>
<kwd>MERS-CoV</kwd>
<kwd>SARS-CoV</kwd>
<kwd>glycopeptide</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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