Novel synthetic antiviral peptides: design, synthesis, physico-chemical analysis and activity

• Artem A. Shatilov
• Anastasia V. Shatilova
• Larisa V. Saprygina
• Marina M. Babikhina
• Ekaterina D. Timotievich
• Valeriia I. Kovchina
• Sergey M. Andreev
• Valery V. Smirnov
• Dmitry A. Kudlay
• Igor P. Shilovskiy
• Musa R. Khaitov

Abstract

Introduction. Currently, there is a high demand for new promising drugs for the treatment of respiratory viral infections. The great deal of these infections, including those leading to life-threatening complications, are caused by human respiratory syncytial virus (RSV). Synthetic peptides are being widely developed and tested as potential antiviral drugs that can be used in treatment of RSV infections as well. Development of new peptides with proposed antiviral activity strongly relies on rational design of their structures and research of their physicochemical properties to determine the correlation between structure and activity.

The aims – to create and experimentally determine structures of new synthetic antiviral peptides, to study their activity against RSV.

Material and methods. The structures of the peptides are based on structural fragments of several nucleolin ligands, the cellular target protein of RSV, as well as on previous results of the authors. The peptides were obtained by solid-phase peptide synthesis, identified with mass spectrometry, quantitated with CHNSO-analysis, their purity was determined by capillary zone electrophoresis. Antiviral activity was determined using a cultured RSV strain in vitro. Cytotoxicity was determined by MTT test.

Results. All synthesized peptides were found to have significant antiviral properties. We assume that the greatest effect is achieved by combining aromatic and cationic amino acid residues in the peptide structure, in particular Y, F, R, K, O. Antiviral effect was demonstrated for dendrimeric peptides as well as for linear. The positive net charge of the peptide and/or pronounced amphipathy contributed to the manifestation of antiviral properties. These particular structural properties are often found in antiviral, cell-penetrating, and antimicrobial peptides, including natural ones.

Conclusion. Five novel antiviral peptides were synthesized, characterized with physico-chemical methods and were found to have significant anti-RSV activity. These peptides can be used in further development of new antiviral peptide drugs. A possible explanation is provided for correlation between the structure of peptides and their activity.

Keywords:synthetic peptides; antiviral peptides; cationic peptides; dendrimer peptides; respiratory syncytial virus; pharmaceutical development

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