Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor
Identifieur interne : 003E65 ( Main/Exploration ); précédent : 003E64; suivant : 003E66Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor
Auteurs : Dong P. Han [États-Unis] ; Adam Penn-Nicholson [États-Unis] ; Michael W. Cho [États-Unis]Source :
- Virology [ 0042-6822 ] ; 2006.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (pharmacologie), Cellules HeLa, Cellules Vero, Conformation des protéines, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (métabolisme), Humains, Modèles moléculaires, Mutagenèse dirigée, Peptidyl-Dipeptidase A (), Peptidyl-Dipeptidase A (génétique), Peptidyl-Dipeptidase A (métabolisme), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (métabolisme), Séquence d'acides aminés, Virus du SRAS (), Virus du SRAS (métabolisme).
- MESH :
- génétique : Peptidyl-Dipeptidase A.
- métabolisme : Glycoprotéines membranaires, Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale, Virus du SRAS.
- pharmacologie : Antiviraux.
- Animaux, Cellules HeLa, Cellules Vero, Conformation des protéines, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Modèles moléculaires, Mutagenèse dirigée, Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale, Séquence d'acides aminés, Virus du SRAS.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antiviral Agents (pharmacology), Chlorocebus aethiops, HeLa Cells, Humans, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (metabolism), Models, Molecular, Mutagenesis, Site-Directed, Peptidyl-Dipeptidase A (chemistry), Peptidyl-Dipeptidase A (genetics), Peptidyl-Dipeptidase A (metabolism), Protein Conformation, SARS Virus (drug effects), SARS Virus (metabolism), Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Peptidyl-Dipeptidase A, Viral Envelope Proteins.
- chemical , genetics : Peptidyl-Dipeptidase A.
- chemical , metabolism : Membrane Glycoproteins, Peptidyl-Dipeptidase A, Viral Envelope Proteins.
- chemical , pharmacology : Antiviral Agents.
- drug effects : SARS Virus.
- metabolism : SARS Virus.
- Amino Acid Sequence, Animals, Chlorocebus aethiops, HeLa Cells, Humans, Models, Molecular, Mutagenesis, Site-Directed, Protein Conformation, Spike Glycoprotein, Coronavirus, Vero Cells.
Abstract
Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, SARS-CoV. Virus entry into cells is mediated through interactions between spike (S) glycoprotein and angiotensin-converting enzyme 2 (ACE2). Alanine scanning mutagenesis analysis was performed to identify determinants on ACE2 critical for SARS-CoV infection. Results indicated that charged amino acids between residues 22 and 57 were important, K26 and D30, in particular. Peptides representing various regions of ACE2 critical for virus infection were chemically synthesized and evaluated for antiviral activity. Two peptides (a.a. 22–44 and 22–57) exhibited a modest antiviral activity with IC50 of about 50 μM and 6 μM, respectively. One peptide comprised of two discontinuous segments of ACE2 (a.a. 22–44 and 351–357) artificially linked together by glycine, exhibited a potent antiviral activity with IC50 of about 0.1 μM. This novel peptide is a promising candidate as a therapeutic agent against this deadly emerging pathogen.
Url:
DOI: 10.1016/j.virol.2006.01.029
PubMed: 16510163
PubMed Central: 7111894
Affiliations:
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Le document en format XML
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Han</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Penn Nicholson, Adam" sort="Penn Nicholson, Adam" uniqKey="Penn Nicholson A" first="Adam" last="Penn-Nicholson">Adam Penn-Nicholson</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Cho, Michael W" sort="Cho, Michael W" uniqKey="Cho M" first="Michael W." last="Cho">Michael W. 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(genetics)</term><term>Peptidyl-Dipeptidase A (metabolism)</term><term>Protein Conformation</term><term>SARS Virus (drug effects)</term><term>SARS Virus (metabolism)</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Cellules HeLa</term><term>Cellules Vero</term><term>Conformation des protéines</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Humains</term><term>Modèles moléculaires</term><term>Mutagenèse dirigée</term><term>Peptidyl-Dipeptidase A ()</term><term>Peptidyl-Dipeptidase A (génétique)</term><term>Peptidyl-Dipeptidase A (métabolisme)</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Séquence d'acides aminés</term><term>Virus du SRAS ()</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Peptidyl-Dipeptidase A</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Peptidyl-Dipeptidase A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Glycoproteins</term><term>Peptidyl-Dipeptidase A</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Peptidyl-Dipeptidase A</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Chlorocebus aethiops</term><term>HeLa Cells</term><term>Humans</term><term>Models, Molecular</term><term>Mutagenesis, Site-Directed</term><term>Protein Conformation</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HeLa</term><term>Cellules Vero</term><term>Conformation des protéines</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Humains</term><term>Modèles moléculaires</term><term>Mutagenèse dirigée</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale</term><term>Séquence d'acides aminés</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, SARS-CoV. Virus entry into cells is mediated through interactions between spike (S) glycoprotein and angiotensin-converting enzyme 2 (ACE2). Alanine scanning mutagenesis analysis was performed to identify determinants on ACE2 critical for SARS-CoV infection. Results indicated that charged amino acids between residues 22 and 57 were important, K26 and D30, in particular. Peptides representing various regions of ACE2 critical for virus infection were chemically synthesized and evaluated for antiviral activity. Two peptides (a.a. 22–44 and 22–57) exhibited a modest antiviral activity with IC<sub>50</sub> of about 50 μM and 6 μM, respectively. One peptide comprised of two discontinuous segments of ACE2 (a.a. 22–44 and 351–357) artificially linked together by glycine, exhibited a potent antiviral activity with IC<sub>50</sub> of about 0.1 μM. This novel peptide is a promising candidate as a therapeutic agent against this deadly emerging pathogen.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abraham, S" uniqKey="Abraham S">S. Abraham</name></author><author><name sortKey="Kienzle, T E" uniqKey="Kienzle T">T.E. Kienzle</name></author><author><name sortKey="Lapps, W" uniqKey="Lapps W">W. Lapps</name></author><author><name sortKey="Brian, D A" uniqKey="Brian D">D.A. Brian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burns, J C" uniqKey="Burns J">J.C. Burns</name></author><author><name sortKey="Friedmann, T" uniqKey="Friedmann T">T. Friedmann</name></author><author><name sortKey="Driever, W" uniqKey="Driever W">W. Driever</name></author><author><name sortKey="Burrascano, M" uniqKey="Burrascano M">M. Burrascano</name></author><author><name sortKey="Yee, J K" uniqKey="Yee J">J.K. 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Gramatikoff</name></author><author><name sortKey="Dimitrov, D S" uniqKey="Dimitrov D">D.S. Dimitrov</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Ohio"><name sortKey="Han, Dong P" sort="Han, Dong P" uniqKey="Han D" first="Dong P." last="Han">Dong P. Han</name></region><name sortKey="Cho, Michael W" sort="Cho, Michael W" uniqKey="Cho M" first="Michael W." last="Cho">Michael W. Cho</name><name sortKey="Cho, Michael W" sort="Cho, Michael W" uniqKey="Cho M" first="Michael W." last="Cho">Michael W. Cho</name><name sortKey="Cho, Michael W" sort="Cho, Michael W" uniqKey="Cho M" first="Michael W." last="Cho">Michael W. Cho</name><name sortKey="Penn Nicholson, Adam" sort="Penn Nicholson, Adam" uniqKey="Penn Nicholson A" first="Adam" last="Penn-Nicholson">Adam Penn-Nicholson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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