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 : 001230 ( Main/Exploration ); précédent : 001229; suivant : 001231Glycopeptide 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.
Descripteurs français
- KwdFr :
- Antibactériens (pharmacologie), Cathepsine L (antagonistes et inhibiteurs), Cathepsine L (métabolisme), Cellules HeLa, Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme), Ebolavirus (génétique), Ebolavirus (métabolisme), Endosomes (enzymologie), Endosomes (génétique), Endosomes (virologie), Fièvre hémorragique à virus Ebola (enzymologie), Fièvre hémorragique à virus Ebola (traitement médicamenteux), Fièvre hémorragique à virus Ebola (épidémiologie), Humains, Lysosomes (enzymologie), Lysosomes (génétique), Lysosomes (virologie), Pénétration virale (), Syndrome respiratoire aigu sévère (enzymologie), Syndrome respiratoire aigu sévère (traitement médicamenteux), Syndrome respiratoire aigu sévère (épidémiologie), Téicoplanine (pharmacocinétique), Virus du SRAS (génétique), Virus du SRAS (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Cathepsine L.
- enzymologie : Endosomes, Fièvre hémorragique à virus Ebola, Lysosomes, Syndrome respiratoire aigu sévère.
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Ebolavirus, Endosomes, Lysosomes, Virus du SRAS.
- métabolisme : Cathepsine L, Coronavirus du syndrome respiratoire du Moyen-Orient, Ebolavirus, Virus du SRAS.
- pharmacocinétique : Téicoplanine.
- pharmacologie : Antibactériens.
- traitement médicamenteux : Fièvre hémorragique à virus Ebola, Syndrome respiratoire aigu sévère.
- virologie : Endosomes, Lysosomes.
- épidémiologie : Fièvre hémorragique à virus Ebola, Syndrome respiratoire aigu sévère.
- Cellules HeLa, Humains, Pénétration virale.
English descriptors
- KwdEn :
- Anti-Bacterial Agents (pharmacology), Cathepsin L (antagonists & inhibitors), Cathepsin L (metabolism), Ebolavirus (genetics), Ebolavirus (metabolism), Endosomes (enzymology), Endosomes (genetics), Endosomes (virology), HeLa Cells, Hemorrhagic Fever, Ebola (drug therapy), Hemorrhagic Fever, Ebola (enzymology), Hemorrhagic Fever, Ebola (epidemiology), Humans, Lysosomes (enzymology), Lysosomes (genetics), Lysosomes (virology), Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (metabolism), SARS Virus (genetics), SARS Virus (metabolism), Severe Acute Respiratory Syndrome (drug therapy), Severe Acute Respiratory Syndrome (enzymology), Severe Acute Respiratory Syndrome (epidemiology), Teicoplanin (pharmacokinetics), Virus Internalization (drug effects).
- MESH :
- chemical , antagonists & inhibitors : Cathepsin L.
- chemical , metabolism : Cathepsin L.
- chemical , pharmacokinetics : Teicoplanin.
- chemical , pharmacology : Anti-Bacterial Agents.
- drug effects : Virus Internalization.
- drug therapy : Hemorrhagic Fever, Ebola, Severe Acute Respiratory Syndrome.
- enzymology : Endosomes, Hemorrhagic Fever, Ebola, Lysosomes, Severe Acute Respiratory Syndrome.
- epidemiology : Hemorrhagic Fever, Ebola, Severe Acute Respiratory Syndrome.
- genetics : Ebolavirus, Endosomes, Lysosomes, Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- metabolism : Ebolavirus, Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- virology : Endosomes, Lysosomes.
- HeLa Cells, Humans.
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
Affiliations:
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Le document en format XML
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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></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="Pan, Ting" sort="Pan, Ting" uniqKey="Pan T" first="Ting" last="Pan">Ting Pan</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="Zhang, Junsong" sort="Zhang, Junsong" uniqKey="Zhang J" first="Junsong" last="Zhang">Junsong 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><author><name sortKey="Li, Qianwen" sort="Li, Qianwen" uniqKey="Li Q" first="Qianwen" last="Li">Qianwen Li</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="Zhang, Xue" sort="Zhang, Xue" uniqKey="Zhang X" first="Xue" last="Zhang">Xue 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><author><name sortKey="Bai, Chuan" sort="Bai, Chuan" uniqKey="Bai C" first="Chuan" last="Bai">Chuan Bai</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="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></author><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></author><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></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anti-Bacterial Agents (pharmacology)</term><term>Cathepsin L (antagonists & inhibitors)</term><term>Cathepsin L (metabolism)</term><term>Ebolavirus (genetics)</term><term>Ebolavirus (metabolism)</term><term>Endosomes (enzymology)</term><term>Endosomes (genetics)</term><term>Endosomes (virology)</term><term>HeLa Cells</term><term>Hemorrhagic Fever, Ebola (drug therapy)</term><term>Hemorrhagic Fever, Ebola (enzymology)</term><term>Hemorrhagic Fever, Ebola (epidemiology)</term><term>Humans</term><term>Lysosomes (enzymology)</term><term>Lysosomes (genetics)</term><term>Lysosomes (virology)</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome (drug therapy)</term><term>Severe Acute Respiratory Syndrome (enzymology)</term><term>Severe Acute Respiratory Syndrome (epidemiology)</term><term>Teicoplanin (pharmacokinetics)</term><term>Virus Internalization (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antibactériens (pharmacologie)</term><term>Cathepsine L (antagonistes et inhibiteurs)</term><term>Cathepsine L (métabolisme)</term><term>Cellules HeLa</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme)</term><term>Ebolavirus (génétique)</term><term>Ebolavirus (métabolisme)</term><term>Endosomes (enzymologie)</term><term>Endosomes (génétique)</term><term>Endosomes (virologie)</term><term>Fièvre hémorragique à virus Ebola (enzymologie)</term><term>Fièvre hémorragique à virus Ebola (traitement médicamenteux)</term><term>Fièvre hémorragique à virus Ebola (épidémiologie)</term><term>Humains</term><term>Lysosomes (enzymologie)</term><term>Lysosomes (génétique)</term><term>Lysosomes (virologie)</term><term>Pénétration virale ()</term><term>Syndrome respiratoire aigu sévère (enzymologie)</term><term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term><term>Syndrome respiratoire aigu sévère (épidémiologie)</term><term>Téicoplanine (pharmacocinétique)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Cathepsin L</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cathepsin L</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Teicoplanin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Bacterial Agents</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Cathepsine L</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Virus Internalization</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Hemorrhagic Fever, Ebola</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Endosomes</term><term>Fièvre hémorragique à virus Ebola</term><term>Lysosomes</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Endosomes</term><term>Hemorrhagic Fever, Ebola</term><term>Lysosomes</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Hemorrhagic Fever, Ebola</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Ebolavirus</term><term>Endosomes</term><term>Lysosomes</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Ebolavirus</term><term>Endosomes</term><term>Lysosomes</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Ebolavirus</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cathepsine L</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Ebolavirus</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Téicoplanine</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antibactériens</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Fièvre hémorragique à virus Ebola</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Endosomes</term><term>Lysosomes</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Endosomes</term><term>Lysosomes</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Fièvre hémorragique à virus Ebola</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" xml:lang="en"><term>HeLa Cells</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules HeLa</term><term>Humains</term><term>Pénétration virale</term></keywords></textClass></profileDesc></teiHeader><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
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