MERS-CoV spike protein: a key target for antivirals.
Identifieur interne : 000D08 ( Main/Curation ); précédent : 000D07; suivant : 000D09MERS-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
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<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>
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