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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
A Fusion Peptide in the Spike Protein of MERS Coronavirus
Entedar A J Alsaadi1, Benjamin W Neuman2, Ian M Jones3
1School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Abstract:
Coronaviruses represent current and emerging threats for many species, including humans. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is responsible for sporadic infections in mostly Middle Eastern countries, with occasional transfer elsewhere. A key step in the MERS-CoV replication cycle is the fusion of the virus and host cell membranes mediated by the virus spike protein, S. The location of the fusion peptide within the MERS S protein has not been precisely mapped. We used isolated peptides and giant unilamellar vesicles (GUV) to demonstrate membrane binding for a peptide located near the N-terminus of the S2 domain. Key residues required for activity were mapped by amino acid replacement and their relevance in vitro tested by their introduction into recombinant MERS S protein expressed in mammalian cells. Mutations preventing membrane binding in vitro also abolished S-mediated syncytium formation consistent with the identified peptide acting as the fusion peptide for the S protein of MERS-CoV.
Insights
Researchers identified the MERS-CoV spike protein
Area of Science:
- Virology
- Molecular Biology
Background:
- Coronaviruses, including Middle East respiratory syndrome-related coronavirus (MERS-CoV), pose significant threats to various species.
- Viral membrane fusion, mediated by the spike (S) protein, is crucial for MERS-CoV replication.
- The precise location of the MERS-CoV S protein's fusion peptide remains unmapped.
Purpose of the Study:
- To map the fusion peptide of the MERS-CoV S protein.
- To elucidate the role of specific residues in viral membrane fusion.
Main Methods:
- Utilized isolated peptides and giant unilamellar vesicles (GUVs) to assess membrane binding.
- Employed amino acid replacement to map key residues essential for fusion peptide activity.
- Tested mutant MERS S proteins expressed in mammalian cells.
Main Results:
- Identified a peptide near the N-terminus of the S2 domain exhibiting membrane-binding activity.
- Determined key residues critical for membrane binding and fusion.
- Demonstrated that mutations impairing membrane binding abolished syncytium formation.
Conclusions:
- The identified peptide functions as the fusion peptide for the MERS-CoV S protein.
- This finding advances understanding of MERS-CoV entry mechanisms.
- Provides insights into potential targets for antiviral strategies.
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