Antimicrobial Activity of Cyclic-Monomeric and Dimeric Derivatives of the Snail-Derived Peptide Cm-p5 against Viral and Multidrug-Resistant Bacterial Strains

• Main Authors: Melaine González-García, Fidel Morales-Vicente, Erbio Díaz Pico, Hilda Garay, Daniel G. Rivera, Mark Grieshober, Lia Raluca Olari, Rüdiger Groß, Carina Conzelmann, Franziska Krüger, Fabian Zech, Caterina Prelli Bozzo, Janis A. Müller, Alexander Zelikin, Heinz Raber, Dennis Kubiczek, Frank Rosenau, Jan Münch, Steffen Stenger, Barbara Spellerberg, Octavio L. Franco, Armando A. Rodriguez Alfonso, Ludger Ständker, Anselmo J. Otero-Gonzalez
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Biomolecules
• Subjects: antimicrobial peptides; Cm-p5; antibacterial activity; multiresistant microorganisms; chemical derivatives
• Online Access: https://www.mdpi.com/2218-273X/11/5/745

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of <i>Candida albicans</i>. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i> <i>Extended Spectrum β-Lactamase</i> (ESBL), and <i>Streptococcus agalactiae</i>, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against <i>Acinetobacter baumanii</i> and <i>Enterococcus faecium</i>. In addition, the two dimers showed a moderate activity against <i>Pseudomonas aeruginosa</i> PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of <i>Mycobacterium tuberculosis</i>, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.