Biophysical and bioinformatic analysis of the amino acid sequence of alloferon

Background. The active ingredient of a new-generation antiviral drug for the treatment of herpes and human papillomavirus infection is alloferon, an oligopeptide with the amino acid sequence HGVSGHGQHGVHG. By inducing interferon biosynthesis, alloferon improves the immune status of men and women with various viral and bacterial-viral infections. The precise mechanism of alloferon's molecular pharmacological action is unknown.

Objective: To establish possible molecular mechanisms of the anti-infective, immunostimulatory, and other effects of alloferon.

Material and methods. Biophysical modeling of the structure and properties of the alloferon oligopeptide and bioinformatic analysis of its amino acid sequence in proteomic databases.

Results. Expert analysis of bioinformatics and biophysical modeling results revealed that the primary hypothesis for alloferon's action is its role as an antigenic epitope, similar in structure to fragments of viral capsid proteins (including hemagglutinin). By interacting with T-cell receptors (TCRs) via major histocompatibility complex (MHC) proteins, alloferon and/or its fragments activate NK lymphocytes, which facilitate the destruction of viral and bacterial pathogens. This mechanism is supported not only by alloferon's similarity to known TCR antigenic epitopes but also by the results of biophysical prediction of epitopes, processing, and binding of alloferon to MHC proteins. The second most significant molecular mechanism involves alloferon's properties as an antimicrobial peptide (AMP) with antiviral activity. This hypothesis is supported by (1) the similarity of the amino acid sequence and amino acid composition of alloferon with known AMPs (piscidins, CA-1, bacteriocin plantaricin, etc.); (2) the potential alpha-helical structure of alloferon; (3) the results of bioinformatics and biophysical prediction of AMP activity against bacterial (E. coli, P. aeruginosa, K. pneumoniae, S. aureus, etc.) and viral (DENV-1, JEV, MERS-CoV, SARS-CoV, SARS-CoV-2, hepatitis C virus, herpes simplex virus) pathogens. Other potentially important molecular mechanisms of action of alloferon include (1) activation of formyl peptide receptors FPR1/2 on the surface of neutrophils (causes chemotaxis of lymphocytes to the site of infection); (2) inhibition of the interleukin-17 receptor (anti-inflammatory effect); (3) blocking the interaction of viruses with sialic acids; (4) cytoprotective properties of peptide fragments within the alloferon molecule; (5) inhibition of proteins containing the potassium channels tetramerization domain (KCTD) (important for modulating neurotransmission and for antitumor activity).

Conclusion. The results of this study indicate verifiable mechanisms of molecular action of alloferon.

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