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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
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Fragments of viral surface proteins modulate innate immune responses via formyl peptide receptors

Heiko Heilmann1, Lukas Busch1, Celine Buchmann1

  • 1Molecular Immunology, Department of Informatics and Microsystems Technology, University of Applied Sciences Kaiserslautern, 66482 Zweibrücken, Germany.

Iscience
|July 24, 2025
PubMed

Insights

Formyl peptide receptors (FPRs) sense viral pathogen motifs on surface proteins, modulating innate immune cell functions. These motifs, found in COVID-19 patients, suggest FPRs broadly impact antiviral responses across diverse viral infections.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Formyl peptide receptors (FPRs) are pattern recognition receptors primarily known for sensing bacterial pathogens.
  • Viral pathogens also possess surface proteins that can interact with the host immune system.

Purpose of the Study:

  • To identify and characterize activator and inhibitor motifs for FPRs on viral surface proteins.
  • To investigate the role of these motifs in modulating innate immune responses during viral infections.

Main Methods:

  • Identification of FPR activator and inhibitor motifs on viral surface proteins.
  • Peptide-based interaction studies with FPR family members.
  • Analysis of viral breakdown products in COVID-19 patients.
  • Correlation of physiochemical properties with protein aggregation hotspots.

Main Results:

  • Activator and inhibitor motifs for FPRs were identified on viral surface proteins.
  • These motifs interact with all FPR family members, modulating innate immune cell functions.
  • Viral breakdown products containing these motifs were detected in COVID-19 patients.
  • Motifs in the spike protein are located in mutagenic or conserved regions, and correlate with protein aggregation hotspots.

Conclusions:

  • FPRs are broadly involved in sensing viral pathogens through specific surface protein motifs.
  • These motifs can modulate innate immune responses, suggesting a general role in antiviral immunity.
  • The findings have implications for understanding host-pathogen interactions in various viral infections, including COVID-19.
Keywords:
Immune responseImmunityVirology

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