Multivalent Display of Antimicrobial Peptides on Plant Virus Scaffolds Enhances Killing of Drug-Resistant Bacteria.

Ahmed Ghouneimy; Shahid Chaudhary; Muhammad Tehseen; Ahmed Saleh; Maged Serag; Maya Ayach; Ebtihaj Bukhari; Maazallah Masood; Kosuke Sakashita; Pei-Ying Hong; Satoshi Habuchi; Samir M Hamdan; Magdy Mahfouz

doi:10.1021/acsnano.6c03117

PubMed · 42302129

Multivalent Display of Antimicrobial Peptides on Plant Virus Scaffolds Enhances Killing of Drug-Resistant Bacteria.

Ahmed Ghouneimy·Shahid Chaudhary·Muhammad Tehseen·Ahmed Saleh·Maged Serag·Maya Ayach·Ebtihaj Bukhari·Maazallah Masood·Kosuke Sakashita·Pei-Ying Hong·Satoshi Habuchi·Samir M Hamdan·Magdy Mahfouz

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Abstract

Multidrug-resistant (MDR) bacteria pose a significant challenge to global health. Antimicrobial peptides (AMPs) have emerged as promising candidates against MDR bacteria due to their rapid and broad-spectrum activity; however, their clinical translation is hindered by compromised activity, toxicity, and poor stability under in vivo conditions. Here, we report the development of RPG (rod-based peptide grids), a plant virus-based antimicrobial platform that harnesses the structural scaffold of high-aspect-ratio Potato virus X (PVX) for the multivalent and modular display of AMPs. Our data show that RPG enhances the efficacy of AMPs by more than 9700-fold, maintaining activity under in vivo salt conditions. RPG eradicates MDR pathogens within 10-30 min, surpassing the efficacy of last-resort antibiotics (vancomycin, tigecycline, and cefiderocol), while exhibiting low measurable cytotoxicity to mammalian cells at high therapeutic doses. Due to structural complexity, RPG demonstrates stability in serum and resistance to proteases. Multivalent display of peptide variants enabled enhanced broad-spectrum killing at low doses. This work establishes plant virus-AMP conjugates as a safe, potent, broad-spectrum antimicrobial platform, offering a versatile strategy for addressing antibiotic resistance.

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Antimicrobial Peptides Anti-Bacterial Agents Microbial Sensitivity Tests Potexvirus MRSA PVX antimicrobial peptides bioproduction multidrug resistance plant virus Journal Article

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Ahmed Ghouneimy, Shahid Chaudhary, Muhammad Tehseen, Ahmed Saleh, Maged Serag, Maya Ayach, Ebtihaj Bukhari, Maazallah Masood, Kosuke Sakashita, Pei-Ying Hong, Satoshi Habuchi, Samir M Hamdan, Magdy Mahfouz. 2026-09-08. Multivalent Display of Antimicrobial Peptides on Plant Virus Scaffolds Enhances Killing of Drug-Resistant Bacteria.. https://doi.org/10.1021/acsnano.6c03117

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