title: MERS-CoV spike protein: a key target for antivirals.
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.
authors.affiliation: a Laboratory of Viral Immunology , Lindsley F. Kimball Research Institute, New York Blood Center , New York , NY , USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN , USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: c State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.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.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: b Department of Pharmacology , University of Minnesota Medical School , Minneapolis , MN , USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: a Laboratory of Viral Immunology , Lindsley F. Kimball Research Institute, New York Blood Center , New York , NY , USA.|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.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D018352:Coronavirus Infections / Q000188:drug therapy* / Q000821:virology; D015195:Drug Design; D006801:Humans; D065207:Middle East Respiratory Syndrome Coronavirus / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D010455:Peptides
keywords: MERS; MERS-CoV; membrane fusion; monoclonal antibodies; peptides; receptor-binding domain; spike protein; therapeutics