Related Experiment Video
Updated: Sep 19, 2025
Author Spotlight: Advancements in Multiplex Detection of Respiratory Viruses
Published on: November 10, 2023
Designed miniproteins potently inhibit and protect against MERS-CoV
Robert J Ragotte1, M Alejandra Tortorici2, Nicholas J Catanzaro3
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Abstract:
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with a 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved for use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins that bind with high affinity to the MERS-CoV spike (S) glycoprotein, the main target of neutralizing antibodies and vaccine development. We show that these miniproteins broadly neutralize a panel of MERS-CoV S variants, spanning the known antigenic diversity of this pathogen, by targeting a conserved site in the receptor-binding domain (RBD). The miniproteins directly compete with binding of the dipeptidylpeptidase 4 (DPP4) receptor to MERS-CoV S, thereby blocking viral attachment to the host entry receptor and subsequent membrane fusion. Intranasal administration of a lead miniprotein provides prophylactic protection against stringent MERS-CoV challenge in mice, motivating its future clinical development as a next-generation countermeasure against this virus with pandemic potential.
Insights
Researchers designed novel miniproteins to neutralize Middle East respiratory syndrome coronavirus (MERS-CoV). These miniproteins target conserved sites on the MERS-CoV spike protein, offering broad protection against variants and blocking viral entry.
Area of Science:
- Virology
- Protein Engineering
- Immunology
Background:
- Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high human case-fatality.
- Current therapeutic and vaccine options for MERS-CoV are limited for both human and camel populations.
Purpose of the Study:
- To computationally design novel miniproteins targeting the MERS-CoV spike glycoprotein.
- To evaluate the broad neutralization capacity and mechanism of action of these miniproteins.
Main Methods:
- Computational design of monomeric and homo-oligomeric miniproteins.
- Affinity assessment for binding to MERS-CoV spike (S) glycoprotein.
- Neutralization assays against diverse MERS-CoV S variants.
- In vivo efficacy studies using intranasal administration in a mouse model.
Main Results:
- Designed miniproteins exhibit high-affinity binding to the MERS-CoV S glycoprotein.
- Miniproteins broadly neutralize MERS-CoV variants by targeting a conserved receptor-binding domain (RBD) site.
- Miniproteins block viral attachment by competing with dipeptidylpeptidase 4 (DPP4) receptor binding.
- Intranasal administration of a lead miniprotein conferred prophylactic protection in a MERS-CoV mouse challenge model.
Conclusions:
- Computationally designed miniproteins represent a promising therapeutic strategy against MERS-CoV.
- These miniproteins offer broad-spectrum neutralization and block viral entry via a conserved mechanism.
- Further clinical development of these miniproteins is warranted as a next-generation countermeasure against MERS-CoV.
More Related Videos
07:53A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
08:40Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
Published on: March 1, 2019
