MERS-CoV spike protein: a key target for antivirals.
Identifieur interne : 000C35 ( PubMed/Checkpoint ); précédent : 000C34; suivant : 000C36MERS-CoV spike protein: a key target for antivirals.
Auteurs : Lanying Du [États-Unis] ; Yang Yang [États-Unis] ; Yusen Zhou [République populaire de Chine] ; Lu Lu [République populaire de Chine] ; Fang Li [États-Unis] ; Shibo Jiang [États-Unis]Source :
- Expert opinion on therapeutic targets [ 1744-7631 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Anticorps monoclonaux (pharmacologie), Anticorps neutralisants (pharmacologie), Antiviraux (pharmacologie), Conception de médicament, Coronavirus du syndrome respiratoire du Moyen-Orient (), Humains, Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (virologie), Peptides (pharmacologie), Pénétration virale ().
- MESH :
- pharmacologie : Anticorps monoclonaux, Anticorps neutralisants, Antiviraux, Peptides.
- traitement médicamenteux : Infections à coronavirus.
- virologie : Infections à coronavirus.
- Animaux, Conception de médicament, Coronavirus du syndrome respiratoire du Moyen-Orient, Humains, Pénétration virale.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (pharmacology), Antibodies, Neutralizing (pharmacology), Antiviral Agents (pharmacology), Coronavirus Infections (drug therapy), Coronavirus Infections (virology), Drug Design, Humans, Middle East Respiratory Syndrome Coronavirus (drug effects), Peptides (pharmacology), Virus Internalization (drug effects).
- MESH :
- chemical , pharmacology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antiviral Agents, Peptides.
- drug effects : Middle East Respiratory Syndrome Coronavirus, Virus Internalization.
- drug therapy : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, Drug Design, Humans.
Abstract
The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. Expert opinion: No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb's limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.
DOI: 10.1080/14728222.2017.1271415
PubMed: 27936982
Affiliations:
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Kimball Research Institute, New York Blood Center , New York , NY , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>a Laboratory of Viral Immunology , Lindsley F. Kimball Research Institute, New York Blood Center , New York , NY </wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name><affiliation wicri:level="2"><nlm:affiliation>b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN </wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation wicri:level="1"><nlm:affiliation>c State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>c State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing </wicri:regionArea><wicri:noRegion>Beijing </wicri:noRegion></affiliation></author><author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><affiliation wicri:level="1"><nlm:affiliation>d Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology , Fudan University , Shanghai , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>d Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology , Fudan University , Shanghai </wicri:regionArea><wicri:noRegion>Shanghai </wicri:noRegion></affiliation></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name><affiliation wicri:level="2"><nlm:affiliation>b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN </wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="2"><nlm:affiliation>a Laboratory of Viral Immunology , Lindsley F. Kimball Research Institute, New York Blood Center , New York , NY , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>a Laboratory of Viral Immunology , Lindsley F. Kimball Research Institute, New York Blood Center , New York , NY </wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">Expert opinion on therapeutic targets</title><idno type="eISSN">1744-7631</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Monoclonal (pharmacology)</term><term>Antibodies, Neutralizing (pharmacology)</term><term>Antiviral Agents (pharmacology)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (virology)</term><term>Drug Design</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Peptides (pharmacology)</term><term>Virus Internalization (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps monoclonaux (pharmacologie)</term><term>Anticorps neutralisants (pharmacologie)</term><term>Antiviraux (pharmacologie)</term><term>Conception de médicament</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Humains</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Infections à coronavirus (virologie)</term><term>Peptides (pharmacologie)</term><term>Pénétration virale ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Neutralizing</term><term>Antiviral Agents</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Anticorps monoclonaux</term><term>Anticorps neutralisants</term><term>Antiviraux</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Drug Design</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Conception de médicament</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Humains</term><term>Pénétration virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. Expert opinion: No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb's limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27936982</PMID><DateCompleted><Year>2017</Year><Month>06</Month><Day>05</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1744-7631</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><Issue>2</Issue><PubDate><Year>2017</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Expert opinion on therapeutic targets</Title><ISOAbbreviation>Expert Opin. Ther. Targets</ISOAbbreviation></Journal><ArticleTitle>MERS-CoV spike protein: a key target for antivirals.</ArticleTitle><Pagination><MedlinePgn>131-143</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/14728222.2017.1271415</ELocationID><Abstract><AbstractText Label="INTRODUCTION" NlmCategory="BACKGROUND">The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. Expert opinion: No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb's limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Du</LastName><ForeName>Lanying</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>a Laboratory of Viral Immunology , Lindsley F. Kimball Research Institute, New York Blood Center , New York , NY , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Yang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Yusen</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>c State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Lu</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>d Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology , Fudan University , Shanghai , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Fang</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Shibo</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>a Laboratory of Viral Immunology , Lindsley F. Kimball Research Institute, New York Blood Center , New York , NY , USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>d Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology , Fudan University , Shanghai , China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI089728</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI098775</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI110700</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AI109094</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>12</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Expert Opin Ther Targets</MedlineTA><NlmUniqueID>101127833</NlmUniqueID><ISSNLinking>1472-8222</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000911">Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010455">Peptides</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000911" MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015195" MajorTopicYN="N">Drug Design</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010455" MajorTopicYN="N">Peptides</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053586" MajorTopicYN="N">Virus Internalization</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">MERS</Keyword><Keyword MajorTopicYN="Y">MERS-CoV</Keyword><Keyword MajorTopicYN="Y">membrane 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sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name></noRegion><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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