Antimicrobial peptides from marine invertebrates are known not only to act like cytotoxic agents, but they also can display some additional activities in mammalian organisms. In particular, these peptides can modulate the complement system as was described for tachyplesin, a peptide from the horseshoe crab. In this work, we investigated the influence on complement activation of the antimicrobial peptide arenicin-1 from the marine polychaete Arenicola marina. To study effects of arenicin on complement activation in human blood serum, we used hemolytic assays of two types, with antibody sensitized sheep erythrocytes and rabbit erythrocytes. Complement activation was also assessed, by the level of C3a production that was measured by ELISA. We found that the effect of arenicin depends on its concentration. At relatively low concentrations the peptide stimulates complement activation and lysis of target erythrocytes, whereas at higher concentrations arenicin acts as a complement inhibitor. A hypothetical mechanism of peptide action is proposed, suggesting its interaction with two complement proteins, C1q and C3. The results lead to the possibility of the development of new approaches for therapy of diseases connected with complement dysregulation, using peptide regulators derived from natural antimicrobial peptides of invertebrates.

Myeloperoxidase is a key factor promoting development of halogenative/oxidative stress under inflammatory conditions. Previously, we have discovered complexes including myeloperoxidase and its physiological inhibitor, ceruloplasmin in blood plasma of patients with inflammatory diseases of different etiology, e.g., atherosclerosis. Studies on regulation of myeloperoxidase activity by ceruloplasmin have shown that hypochlorous acid, a specific product of myeloperoxidase action, is likely to modify ceruloplasmin during inflammation. The present study was aimed for analysis of relationships between the myeloperoxidase activity, native, and HOCl-modified ceruloplasmin levels in blood plasma samples of the patients with cardiovascular diseases.Specific antibodies against myeloperoxidase, ceruloplasmin, and HOCl-modified ceruloplasmin were obtained and specific enzyme-linked immunosorbent assays (ELISA) were developed. A combination of highly sensitive methods of myeloperoxidase assay i.e., solid-phase adsorption of antigens with subsequent testing of either their activity, or peroxidase-labeled antibody activity allowed elaborating the highly sensitive assays for ceruloplasmin and its HOCl-modified molecules, and for myeloperoxidase (concentration, peroxidase and halogenating activity). Positive correlation was proven between the myeloperoxidase concentration and activities. HOCl-modified ceruloplasmin content also correlated with myeloperoxidase activity.The HOCl-modified ceruloplasmin was first discovered in blood plasma samples from patients with cardiovascular diseases. In view of correlation between myeloperoxidase activity and HOCl-modified ceruloplasmin content in plasma, we suggest that HOCl production is aimed for suppression of myeloperoxidaseinhibitory function of ceruloplasmin.

COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control of the spread of new variants can be achieved through targeting of conserved viral epitopes. In this regard, the SARS-CoV-2 nucleocapsid (N) protein, which is much more conserved than the evolutionarily influenced spike protein (S), is a suitable antigen. The recombinant N protein can be considered not only as a screening antigen but also as a basis for the development of next-generation COVID-19 vaccines, but little is known about induction of antibodies against the N protein via different SARS-CoV-2 variants. In addition, it is important to understand how antibodies produced against the antigen of one variant can react with the N proteins of other variants. Here, we used recombinant N proteins from five SARS-CoV-2 strains to investigate their immunogenicity and antigenicity in a mouse model and to obtain and characterize a panel of hybridoma-derived monoclonal anti-N antibodies. We also analyzed the variable epitopes of the N protein that are potentially involved in differential recognition of antiviral antibodies. These results will further deepen our knowledge of the cross-reactivity of the humoral immune response in COVID-19.

Antimicrobial peptides (AMPs) are not only cytotoxic towards host pathogens or cancer cells but also are able to act as immunomodulators. It was shown that some human and non-human AMPs can interact with complement proteins and thereby modulate complement activity. Thus, AMPs could be considered as the base for complement-targeted therapeutics development. Arenicins from the sea polychaete Arenicola marina, the classical example of peptides with a β-hairpin structure stabilized by a disulfide bond, were shown earlier to be among the most prospective regulators. Here, we investigate the link between arenicins’ structure and their antimicrobial, hemolytic and complement-modulating activities using the derivative Ar-1-(C/A) without a disulfide bond. Despite the absence of this bond, the peptide retains all important functional activities and also appears less hemolytic in comparison with the natural forms. These findings could help to investigate new complement drugs for regulation using arenicin derivatives.

Observations of gamma rays up to several 100 TeV are particularly important to spectrally resolve the cutoff regime of the long-sought Pevatrons, the cosmic-ray PeV accelerators. One component of the TAIGA hybrid detector is the TAIGA-HiSCORE timing array, which currently consists of 28 wide angle (0.6 sr) air Cherenkov timing stations distributed on an area of 0.25 km2. The HiSCORE concept is based on (non-imaging) air shower front sampling with Cherenkov light. First results are presented.

Cationic antimicrobial peptides (CAMPs) have gained attention as promising antimicrobial therapeutics causing lower or no bacterial resistance. Considerable achievements have been made in designing new CAMPs that are highly active as antimicrobials. However, there is a lack of research on their interaction with biologically important proteins. This study focused on CAMPs’ effects on myeloperoxidase (MPO), an enzyme which is microbicidal and concomitantly damaging to host biomolecules and cells due to its ability to produce reactive oxygen and halogen species (ROS/RHS). Four CAMPs designed by us were employed. MPO catalytic activity was assessed by an absorbance spectra analysis and by measuring enzymatic activity using Amplex Red- and Celestine Blue B-based assays. The peptide Hm-AMP2 accelerated MPO turnover. Pept_1545 and Hm-AMP8 inhibited both the MPO chlorinating and peroxidase activities, with components of different inhibition types. Hm-AMP8 was a stronger inhibitor. Its K_i towards H₂O₂ and Cl^– was 0.3–0.4 μM vs. 11–20 μM for pept_1545. Peptide tyrosine and cysteine residues were involved in the mechanisms of the observed effects. The results propose a possible dual role of CAMPs as both antimicrobial agents and agents that downregulate MPO activation, and suggest CAMPs as prototypes for the development of antioxidant compounds to prevent MPO-mediated ROS/RHS overproduction.