Bacterial infections are a prevalent complication after primary viral respiratory infections and are associated with high morbidity and mortality. Antibiotics are widely used against bacterial respiratory pathogens; however, the rise in antibiotic-resistant strains urges us to search for new antimicrobial compounds, including ones that act synergistically with antibiotics. In this study, the minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations of a polyphenol-rich complex of green propolis, Tabebuia avellanedae bark, and Olea europaea leaf extracts against Staphylococcus aureus, Haemophilus influenzae, and Klebsiella pneumoniae were determined, followed by an analysis of the synergistic effect with clarithromycin, azithromycin, and amoxiclav (875/125 mg amoxicillin/clavulanic acid). A combination of extracts showed activity against all three bacterial strains, with MIC values ranging from 0.78 to 12.5 mg/mL and MBC values from 1.56 to 12.5 mg/mL. The extracts showed synergistic activity with azithromycin and clarithromycin against S. aureus, with clarithromycin against K. pneumoniae, and with all three tested antibiotics against H. influenzae. Synergy with clarithromycin was additionally evaluated in a time-kill assay where the synergistic effects against S. aureus and K. pneumoniae were seen within the first 6 h of incubation. The results show the potential of polyphenol-rich extracts in enhancing the efficacy of antibiotic therapy and indicate their potential to be used in the management of respiratory infections.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses mRNA capping to evade the human immune system. The cap formation is performed by the SARS-CoV-2 mRNA cap methyltransferases (MTases) nsp14 and nsp16, which are emerging targets for the development of broad-spectrum antiviral agents. Here, we report results from high-throughput virtual screening against these two enzymes. The docking of seven million commercially available drug-like compounds and S-adenosylmethionine (SAM) co-substrate analogues against both MTases resulted in 80 virtual screening hits (39 against nsp14 and 41 against nsp16), which were purchased and tested using an enzymatic homogeneous time-resolved fluorescent energy transfer (HTRF) assay. Nine compounds showed micromolar inhibition activity (IC₅₀ < 200 μM). The selectivity of the identified inhibitors was evaluated by cross-checking their activity against human glycine N-methyltransferase. The majority of the compounds showed poor selectivity for a specific MTase, no cytotoxic effects, and rather poor cell permeability. Nevertheless, the identified compounds represent good starting points that have the potential to be developed into efficient viral MTase inhibitors.

For sustainable sea buckthorn (Hippophae rhamnoides) berry production, the task at hand is to find an application for the large amount of biomass waste arising at harvesting. Sea buckthorn (SBT) vegetation is currently poorly studied. The purpose of this research was to assess the composition and potential of SBT twigs as a source of valuable biologically active substances. Water and 50% EtOH extracts of twigs of three Latvian SBT cultivars with a high berry yield and quality, popular for cultivation in many countries (H. rhamnoides ‘Maria Bruvele’, ‘Tatiana’, ‘Botanicheskaya Lubitelskaya’), were investigated for the first time. The phytochemical composition (UHPLC-ESI-MS/MS analysis) and biological activity of the obtained hydrophilic extracts were determined. The highest yield of polyphenolic compounds and serotonin was observed for ‘Maria Bruvele’. Hydrophilic extracts were investigated for radical scavenging activity (DPPH˙ test), antibacterial/antifungal activity against five pathogenic bacteria/yeast, cytotoxicity, and the enzymatic activity of alpha-amylase (via in vitro testing), which is extremely important for the treatment of people with underweight, wasting, and malabsorption. The results showed a high potential of sea buckthorn biomass as a source of valuable biologically active compounds for the creation of preparations for the food industry, nutraceuticals, and cosmetics.

It has now been proven that many pathogens that cause infections and inflammation gradually mutate and become resistant to antibiotics. Chemically synthesized drugs treating inflammation most often only affect symptoms, but side effects could lead to the failure of human organs’ functionality. On the other hand, plant-derived natural compounds have a long-term healing effect. It was shown that sea buckthorn (SBT) twigs are a rich source of biologically active compounds, including oligomeric proanthocyanidins (PACs). This study aimed to assess the anti-pathogenic and anti-inflammatory activity of water/ethanol extracts and PACs obtained from the lignocellulosic biomass of eight SBT cultivars. The anti-pathogenic activity of extracts and PACs was studied against pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Bacillus cereus and fungus Candida albicans in 96-well plates by the two-fold serial broth microdilution method. The anti-bacterial activity of purified PACs was 4 and 10 times higher than for water and water/ethanol extracts, respectively, but the extracts had higher anti-fungal activity. Purified PACs showed the ability to reduce IL-8 and IL-6 secretion from poly-I:C-stimulated peripheral blood mononuclear cells. For the extracts and PACs of SBT cultivar ‘Maria Bruvele’ in the concentration range 0.0313–4.0 mg/mL, no toxic effect was observed.

SARS-CoV-2 nsp14 guanine-N7-methyltransferase plays an important role in the viral RNA translation process by catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to viral mRNA cap. We report a structure-guided design and synthesis of 3-(adenosylthio)benzoic acid derivatives as nsp14 methyltransferase inhibitors resulting in compound 5p with subnanomolar inhibitory activity and improved cell membrane permeability in comparison with the parent inhibitor. Compound 5p acts as a bisubstrate inhibitor targeting both SAM and mRNA-binding pockets of nsp14. While the selectivity of 3-(adenosylthio)benzoic acid derivatives against human glycine N-methyltransferase was not improved, the discovery of phenyl-substituted analogs 5p,t may contribute to further development of SARS-CoV-2 nsp14 bisubstrate inhibitors.

The reduction of tissue cytotoxicity and the improvement of cell viability are of utmost significance, particularly in the realm of green chemistry. Despite substantial progress, the threat of local infections remains a concern. Therefore, hydrogel systems that provide mechanical support and a harmonious balance between antimicrobial efficacy and cell viability are greatly needed. Our study explores the preparation of physically crosslinked, injectable, and antimicrobial hydrogels using biocompatible hyaluronic acid (HA) and antimicrobial ε-polylysine (ε-PL) in different weight ratios (10 wt% to 90 wt%). The crosslinking was achieved by forming a polyelectrolyte complex between HA and ε-PL. The influence of HA content on the resulting HA/ε-PL hydrogel physicochemical, mechanical, morphological, rheological, and antimicrobial properties was evaluated, followed by an inspection of their in vitro cytotoxicity and hemocompatibility. Within the study, injectable, self-healing HA/ε-PL hydrogels were developed. All hydrogels showed antimicrobial properties against S. aureus, P. aeruginosa, E. coli, and C. albicans, where HA/ε-PL 30:70 (wt%) composition reached nearly 100% killing efficiency. The antimicrobial activity was directly proportional to ε-PL content in the HA/ε-PL hydrogels. A decrease in ε-PL content led to a reduction of antimicrobial efficacy against S. aureus and C. albicans. Conversely, this decrease in ε-PL content in HA/ε-PL hydrogels was favourable for Balb/c 3T3 cells, leading to the cell viability of 152.57% for HA/ε-PL 70:30 and 142.67% for HA/ε-PL 80:20. The obtained results provide essential insights into the composition of the appropriate hydrogel systems able to provide not only mechanical support but also the antibacterial effect, which can offer opportunities for developing new, patient-safe, and environmentally friendly biomaterials.