Antimicrobial Activity of Cyclic-Monomeric and Dimeric Derivatives of the Snail-Derived Peptide Cm-p5 against Viral and Multidrug-Resistant Bacterial Strains
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
Affiliations
Melaine González-García
Center for Protein Studies, Faculty of Biology, University of Havana, 25 St, La Habana 10400, Cuba
Fidel Morales-Vicente
General Chemistry Department, Faculty of Chemistry and Center for Natural Products Research, Faculty of Chemistry, University of Havana, Zapata street, La Habana 10400, Cuba
Erbio Díaz Pico
Synthetic Peptides Group, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, La Habana 10600, Cuba
Hilda Garay
Synthetic Peptides Group, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, La Habana 10600, Cuba
Daniel G. Rivera
Faculty of Chemistry, Havana University, Zapata Street, La Habana 10400, Cuba
Mark Grieshober
Institute of Medical Microbiology and Hygiene, University Clinic of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Lia Raluca Olari
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Rüdiger Groß
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Carina Conzelmann
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Franziska Krüger
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Fabian Zech
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Caterina Prelli Bozzo
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Janis A. Müller
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Alexander Zelikin
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark
Heinz Raber
Institute of Pharmaceutical Biotechnology, Ulm University, 89081 Ulm, Germany
Dennis Kubiczek
Institute of Pharmaceutical Biotechnology, Ulm University, 89081 Ulm, Germany
Frank Rosenau
Institute of Pharmaceutical Biotechnology, Ulm University, 89081 Ulm, Germany
Jan Münch
Institute of Molecular Virology, University Clinic of Ulm, Meyerhofstrasse. 1, 89081 Ulm, Germany
Steffen Stenger
Institute of Medical Microbiology and Hygiene, University Clinic of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Barbara Spellerberg
Institute of Medical Microbiology and Hygiene, University Clinic of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Octavio L. Franco
Department of Biotechnology, Catholic University Dom Bosco, Campo Grande and Center for Biochemical and Proteomics Analyses, Catholic University of Brasilia, Brasilia, DF 71966-700, Brazil
Armando A. Rodriguez Alfonso
Core Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, Germany
Ludger Ständker
Core Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, Germany
Anselmo J. Otero-Gonzalez
Center for Protein Studies, Faculty of Biology, University of Havana, 25 St, La Habana 10400, Cuba
Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. 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 Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, 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.
