Oxana Galzitskaya1,2
1 Gamaleya Research Centre of Epidemiology and Microbiology, Moscow, Russia
2 Institute of Protein Research, Russian Academy of Sciences, Pushchino, Russia
ogalzit [at] vega.protres.ru
Abstract
Some proteins and peptides are known to have antimicrobial and amyloidogenic properties. Understanding the mechanism of aggregation can be used to combat bacterial and viral diseases.
Using modern data on the process of formation of amyloid structures, we have developed and successfully tested amyloidogenic antimicrobial peptides (AAMPs) with a new mechanism of antimicrobial action – “protein knockout”. This mechanism is based on the principle of directed coaggregation of AAMP and bacterial ribosomal protein S1. The innovative peptide interacts with the target protein of model or pathogenic bacteria, forming aggregates and removing this protein, which is essential for the life of the bacteria, from its working state. During the work, the antimicrobial effects of the developed peptides were examined on two model organisms (Thermus thermophilus and Escherichia coli) and two pathogenic microorganisms (Staphylococcus aureus and Pseudomonas aeruginosa).
Since the emergence of the original variant in Wuhan in 2019, many different variants of SARS-CoV-2 have been described and characterized, varying in transmissibility and pathogenicity in the human population, although the molecular basis of this difference remains controversial. Thus, the Omicron variant is known for its contagiousness, trans-missibility, and lower pathogenicity (mortality). A significant role in this is played by amino acid substitutions on the surface of the Spike protein, which interact with the ACE2 receptor, which can facilitate the penetration of the virus into the cell or help it to evade the immune response. Mutations in this strain result in increased amyloidogenicity of the Omicron strain in the ACE2 receptor binding regions, resulting in an increase in the strength of this interaction for the Omicron BA.1 RBD compared to the Wuhan-Hu-1 or Delta RBD, and this effect was more pronounced at pH 5. This result is associated with Omicron variants’ increased ability to spread through the population.
Keywords: amyloids, antimicrobial peptide, amyloidogenic regions, spike protein