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Discovery of potent measles virus fusion inhibitor peptides via structure-guided derivatization

Ziwei Gao1, Jiei Sasaki2, Tateki Suzuki2

  • 1Depratement of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo Tokyo 113-8656 Japan ssando@chembio.t.u-tokyo.ac.jp jmorimoto@chembio.t.u-tokyo.ac.jp.

RSC Medicinal Chemistry
|February 10, 2025
PubMed

Insights

Researchers developed a novel fusion inhibitor peptide (FIP) derivative to combat measles virus (MeV) infection. This improved FIP derivative shows enhanced binding affinity and strong inhibitory activity against the MeV fusion protein, offering a promising therapeutic candidate.

Area of Science:

  • Virology
  • Drug Discovery
  • Structural Biology

Background:

  • Measles virus (MeV) infection poses a significant health concern.
  • Fusion inhibitor peptides (FIPs) are known to inhibit MeV-induced membrane fusion.
  • Existing FIPs require optimization for enhanced therapeutic efficacy.

Purpose of the Study:

  • To improve the inhibitory activity of FIP against MeV.
  • To conduct a structure-activity relationship (SAR) study of FIP.
  • To design and discover novel FIP derivatives with enhanced anti-MeV properties.

Main Methods:

  • Performed a structure-activity relationship (SAR) study of FIP.
  • Utilized the crystal structure of the MeV fusion protein complex.
  • Designed and synthesized FIP derivatives based on SAR and structural data.

Main Results:

  • Identified an FIP derivative with significantly enhanced inhibitory activity (IC50 = 210 nM).
  • The derivative exhibited improved binding affinity (KD = 6.6 nM) to the MeV fusion protein.
  • Structure-activity relationship analysis guided the design of potent inhibitors.

Conclusions:

  • The developed FIP derivative represents a promising drug candidate for MeV infection treatment.
  • Enhanced binding affinity to the MeV fusion protein is key to improved inhibitory activity.
  • Further development of FIP derivatives could lead to effective antiviral therapies for measles.

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