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 : 000C49 ( PubMed/Checkpoint ); précédent : 000C48; suivant : 000C50Glycopeptide 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 [République populaire de Chine] ; Chao Liu ; Liang Tao ; Hui Zhang [République populaire de Chine]Source :
- The Journal of biological chemistry [ 1083-351X ] ; 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 nm 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.
DOI: 10.1074/jbc.M116.716100
PubMed: 26953343
Affiliations:
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Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>the Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510182, Guangdong, and.</nlm:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Zhang, Jianhua" sort="Zhang, Jianhua" uniqKey="Zhang J" first="Jianhua" last="Zhang">Jianhua Zhang</name><affiliation wicri:level="1"><nlm:affiliation>the CAS Key Laboratory for Pathogenic Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>the CAS Key Laboratory for Pathogenic Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Liu, Chao" sort="Liu, Chao" uniqKey="Liu C" first="Chao" last="Liu">Chao Liu</name><affiliation><nlm:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>Department of Pharmacology, Zhongshan School of Medicine.</nlm:affiliation><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 wicri:level="1"><nlm:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong, zhangh92@mail.sysu.edu.cn.</nlm:affiliation><country wicri:rule="url">République populaire de Chine</country><wicri:regionArea>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26953343</idno><idno type="pmid">26953343</idno><idno type="doi">10.1074/jbc.M116.716100</idno><idno type="wicri:Area/PubMed/Corpus">000C87</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000C87</idno><idno type="wicri:Area/PubMed/Curation">000C87</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000C87</idno><idno type="wicri:Area/PubMed/Checkpoint">000C49</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C49</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">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).</title><author><name sortKey="Zhou, Nan" sort="Zhou, Nan" uniqKey="Zhou N" first="Nan" last="Zhou">Nan Zhou</name><affiliation><nlm:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>the Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510182, Guangdong, and.</nlm:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Zhang, Jianhua" sort="Zhang, Jianhua" uniqKey="Zhang J" first="Jianhua" last="Zhang">Jianhua Zhang</name><affiliation wicri:level="1"><nlm:affiliation>the CAS Key Laboratory for Pathogenic Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>the CAS Key Laboratory for Pathogenic Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Liu, Chao" sort="Liu, Chao" uniqKey="Liu C" first="Chao" last="Liu">Chao Liu</name><affiliation><nlm:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</nlm:affiliation><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:affiliation>Department of Pharmacology, Zhongshan School of Medicine.</nlm:affiliation><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 wicri:level="1"><nlm:affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong, zhangh92@mail.sysu.edu.cn.</nlm:affiliation><country wicri:rule="url">République populaire de Chine</country><wicri:regionArea>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2016" type="published">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">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 nm 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. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26953343</PMID><DateCompleted><Year>2016</Year><Month>11</Month><Day>03</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>28</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1083-351X</ISSN><JournalIssue CitedMedium="Internet"><Volume>291</Volume><Issue>17</Issue><PubDate><Year>2016</Year><Month>Apr</Month><Day>22</Day></PubDate></JournalIssue><Title>The Journal of biological chemistry</Title><ISOAbbreviation>J. Biol. Chem.</ISOAbbreviation></Journal><ArticleTitle>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).</ArticleTitle><Pagination><MedlinePgn>9218-32</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1074/jbc.M116.716100</ELocationID><Abstract><AbstractText>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 nm 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. </AbstractText><CopyrightInformation>© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Ting</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Junsong</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qianwen</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xue</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bai</LastName><ForeName>Chuan</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Feng</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Tao</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>the Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510182, Guangdong, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Jianhua</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>the CAS Key Laboratory for Pathogenic Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Chao</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tao</LastName><ForeName>Liang</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, Zhongshan School of Medicine.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Hui</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>From the Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, and Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou 510080, Guangdong, zhangh92@mail.sysu.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>03</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Biol Chem</MedlineTA><NlmUniqueID>2985121R</NlmUniqueID><ISSNLinking>0021-9258</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>61036-62-2</RegistryNumber><NameOfSubstance UI="D017334">Teicoplanin</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.22.15</RegistryNumber><NameOfSubstance UI="C534281">CTSL protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.22.15</RegistryNumber><NameOfSubstance UI="D056668">Cathepsin L</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056668" MajorTopicYN="N">Cathepsin L</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D029043" MajorTopicYN="N">Ebolavirus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011992" MajorTopicYN="N">Endosomes</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006367" MajorTopicYN="N">HeLa Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019142" MajorTopicYN="N">Hemorrhagic Fever, Ebola</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008247" MajorTopicYN="N">Lysosomes</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045169" MajorTopicYN="N">Severe Acute Respiratory Syndrome</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017334" MajorTopicYN="N">Teicoplanin</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053586" MajorTopicYN="N">Virus Internalization</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Ebola virus</Keyword><Keyword MajorTopicYN="N">MERS-CoV</Keyword><Keyword MajorTopicYN="N">SARS-CoV</Keyword><Keyword MajorTopicYN="N">antibiotics</Keyword><Keyword MajorTopicYN="N">glycopeptide</Keyword><Keyword MajorTopicYN="N">glycoprotein</Keyword><Keyword MajorTopicYN="N">lysosome</Keyword><Keyword MajorTopicYN="N">virus entry</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>01</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>3</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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