Humanizing plant-derived snakins and their encrypted antimicrobial peptides

Area of Science:

• Biochemistry and Molecular Biology
• Plant Science
• Pharmacology

Background:

• Plant-derived antimicrobial peptides (AMPs) require optimization for safe oral consumption and therapeutic use.
• Snakins, a class of cysteine-rich proteins, are being investigated for their diverse biological activities.

Purpose of the Study:

• To identify optimal snakins for oral consumption as preservatives.
• To discover potent, non-toxic AMP fragments for parenteral therapeutic applications.

Main Methods:

• Analysis of 175 GASA-domain-containing snakins, evaluating properties like charge, hydrophobicity, and therapeutic index.
• Virtual digestion to predict oral effects.
• Directed mutagenesis to create non-toxic AMP fragments with retained antimicrobial properties.
• Characterization of promising 20-mer AMPs for properties like cell penetration, antimicrobial activity, and therapeutic potential.

Main Results:

• Snakins from Cajanus cajan, Cucumis melo, Durio zibethinus, Glycine soja, Herrania umbratica, and Ziziphus jujuba were optimal for oral use, showing antihypertensive and antidiabetic potential.
• Modified 20-mer snakin fragments demonstrated cell-penetrating peptide (CPP) properties, including BBB permeation, gram-negative bacterial activity, anti-HIV, anti-HCV, anti-angiogenic, and immunomodulatory effects.
• Specific promising candidates include Mr-SNK2-1a, Na-SNK2-2a(C18W), Na-SNK2-2b(C16F), Cc-SNK1-2a, Si-SNK2-3a(C17P), and Cme-SNK2-1a(C11F).

Conclusions:

• Optimized snakins can serve as safe oral preservatives with additional health benefits.
• Engineered snakin fragments represent promising biotherapeutics for parenteral administration, targeting infections, viral diseases, cancer, and immune modulation.
• Cysteine-rich peptides offer a versatile platform for developing novel therapeutic agents.