TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds.
Identifieur interne : 002431 ( Main/Exploration ); précédent : 002430; suivant : 002432TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds.
Auteurs : Shiori Haga [Japon] ; Noriyo Nagata ; Tadashi Okamura ; Norio Yamamoto ; Tetsutaro Sata ; Naoki Yamamoto ; Takehiko Sasazuki ; Yukihito IshizakaSource :
- Antiviral research [ 1872-9096 ] ; 2010.
Descripteurs français
- KwdFr :
- Acides hydroxamiques (pharmacologie), Animaux, Antienzymes (pharmacologie), Antiviraux (pharmacologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (physiologie), Humains, Lignée cellulaire, Peptidyl-Dipeptidase A (métabolisme), Poumon (anatomopathologie), Poumon (virologie), Protéine ADAM17, Protéines ADAM (antagonistes et inhibiteurs), Protéines ADAM (biosynthèse), Protéines de l'enveloppe virale (physiologie), Pénétration virale, Récepteurs viraux (métabolisme), Souris, Souris de lignée C57BL, Virus du SRAS (pathogénicité).
- MESH :
- anatomopathologie : Poumon.
- antagonistes et inhibiteurs : Protéines ADAM.
- biosynthèse : Protéines ADAM.
- métabolisme : Peptidyl-Dipeptidase A, Récepteurs viraux.
- pathogénicité : Virus du SRAS.
- pharmacologie : Acides hydroxamiques, Antienzymes, Antiviraux.
- physiologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- virologie : Poumon.
- Animaux, Glycoprotéine de spicule des coronavirus, Humains, Lignée cellulaire, Protéine ADAM17, Pénétration virale, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- ADAM Proteins (antagonists & inhibitors), ADAM Proteins (biosynthesis), ADAM17 Protein, Animals, Antiviral Agents (pharmacology), Cell Line, Enzyme Inhibitors (pharmacology), Humans, Hydroxamic Acids (pharmacology), Lung (pathology), Lung (virology), Membrane Glycoproteins (physiology), Mice, Mice, Inbred C57BL, Peptidyl-Dipeptidase A (metabolism), Receptors, Virus (metabolism), SARS Virus (pathogenicity), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (physiology), Virus Internalization.
- MESH :
- chemical , antagonists & inhibitors : ADAM Proteins.
- chemical , biosynthesis : ADAM Proteins.
- chemical , metabolism : Peptidyl-Dipeptidase A, Receptors, Virus.
- chemical , pharmacology : Antiviral Agents, Enzyme Inhibitors, Hydroxamic Acids.
- chemical , physiology : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical : ADAM17 Protein, Spike Glycoprotein, Coronavirus.
- pathogenicity : SARS Virus.
- pathology : Lung.
- virology : Lung.
- Animals, Cell Line, Humans, Mice, Mice, Inbred C57BL, Virus Internalization.
Abstract
Because outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) might reemerge, identifying antiviral compounds is of key importance. Previously, we showed that the cellular factor TNF-alpha converting enzyme (TACE), activated by the spike protein of SARS-CoV (SARS-S protein), was positively involved in viral entry, implying that TACE is a possible target for developing antiviral compounds. To demonstrate this possibility, we here tested the effects of TACE inhibitors on viral entry. In vitro and in vivo data revealed that the TACE inhibitor TAPI-2 attenuated entry of both pseudotyped virus expressing the SARS-S protein in a lentiviral vector backbone and infectious SARS-CoV. TAPI-2 blocked both the SARS-S protein-induced shedding of angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV, and TNF-alpha production in lung tissues. Since the downregulation of ACE2 by SARS-S protein was proposed as an etiological event in the severe clinical manifestations, our data suggest that TACE antagonists block SARS-CoV infection and also attenuate its severe clinical outcome.
DOI: 10.1016/j.antiviral.2009.12.001
PubMed: 19995578
Affiliations:
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ADAM17</term><term>Pénétration virale</term><term>Souris</term><term>Souris de lignée C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Because outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) might reemerge, identifying antiviral compounds is of key importance. Previously, we showed that the cellular factor TNF-alpha converting enzyme (TACE), activated by the spike protein of SARS-CoV (SARS-S protein), was positively involved in viral entry, implying that TACE is a possible target for developing antiviral compounds. To demonstrate this possibility, we here tested the effects of TACE inhibitors on viral entry. In vitro and in vivo data revealed that the TACE inhibitor TAPI-2 attenuated entry of both pseudotyped virus expressing the SARS-S protein in a lentiviral vector backbone and infectious SARS-CoV. TAPI-2 blocked both the SARS-S protein-induced shedding of angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV, and TNF-alpha production in lung tissues. Since the downregulation of ACE2 by SARS-S protein was proposed as an etiological event in the severe clinical manifestations, our data suggest that TACE antagonists block SARS-CoV infection and also attenuate its severe clinical outcome.</div></front></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><noCountry><name sortKey="Ishizaka, Yukihito" sort="Ishizaka, Yukihito" uniqKey="Ishizaka Y" first="Yukihito" last="Ishizaka">Yukihito Ishizaka</name><name sortKey="Nagata, Noriyo" sort="Nagata, Noriyo" uniqKey="Nagata N" first="Noriyo" last="Nagata">Noriyo Nagata</name><name sortKey="Okamura, Tadashi" sort="Okamura, Tadashi" uniqKey="Okamura T" first="Tadashi" last="Okamura">Tadashi Okamura</name><name sortKey="Sasazuki, Takehiko" sort="Sasazuki, Takehiko" uniqKey="Sasazuki T" first="Takehiko" last="Sasazuki">Takehiko Sasazuki</name><name sortKey="Sata, Tetsutaro" sort="Sata, Tetsutaro" uniqKey="Sata T" first="Tetsutaro" last="Sata">Tetsutaro Sata</name><name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name><name sortKey="Yamamoto, Norio" sort="Yamamoto, Norio" uniqKey="Yamamoto N" first="Norio" last="Yamamoto">Norio Yamamoto</name></noCountry><country name="Japon"><region name="Région de Kantō"><name sortKey="Haga, Shiori" sort="Haga, Shiori" uniqKey="Haga S" first="Shiori" last="Haga">Shiori Haga</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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