Rationally optimized mucroporin-M1 peptides disrupt viral envelopes and resist degradation

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Viral infections pose a growing global health threat, necessitating novel broad-spectrum antiviral therapies.
• Peptide therapeutics, like mucroporin-M1 from scorpion venom, show promise due to targeted action and low toxicity.

Purpose of the Study:

• To design, synthesize, and characterize mucroporin-M1 analogues with enhanced helical stability and proteolytic resistance.
• To evaluate the antiviral efficacy and cytotoxicity of these modified peptides.

Main Methods:

• Incorporation of alpha-aminoisobutyric acid (Aib) residues and N-terminal lipidation into mucroporin-M1 structure.
• Structural analysis using circular dichroism (CD) and Nuclear Magnetic Resonance (NMR).
• Assessment of enzymatic degradation resistance, membranolytic activity, and virucidal effects against various viruses.

Main Results:

• Modified analogues exhibited enhanced amphipathic helical conformations, improved stability against enzymatic breakdown, and increased membranolytic activity.
• Several analogues demonstrated potent virucidal activity against enveloped RNA and DNA viruses (Flaviviridae, Herpesviridae) with minimal cytotoxicity.
• No activity was observed against non-enveloped viruses.

Conclusions:

• Chemically optimized mucroporin-M1 analogues possess significant broad-spectrum virucidal potential.
• These modified peptides are promising candidates for developing new peptide-based antiviral drugs.
• The study highlights the therapeutic potential of engineered scorpion-derived peptides against viral pathogens.