No abstract

The coronavirus SARS-CoV-2 is the causative agent for the disease COVID-19. To capture the IgA, IgG, and IgM antibody response of patients infected with SARS-CoV-2 at individual epitope resolution, we constructed planar microarrays of 648 overlapping peptides that cover the four major structural proteins S(pike), N(ucleocapsid), M(embrane), and E(nvelope). The arrays were incubated with sera of 67 SARS-CoV-2 positive and 22 negative control samples. Specific responses to SARS-CoV-2 were detectable, and nine peptides were associated with a more severe course of the disease. A random forest model disclosed that antibody binding to 21 peptides, mostly localized in the S protein, was associated with higher neutralization values in cellular anti-SARS-CoV-2 assays. For antibodies addressing the N-terminus of M, or peptides close to the fusion region of S, protective effects were proven by antibody depletion and neutralization assays. The study pinpoints unusual viral binding epitopes that might be suited as vaccine candidates .

Eight analogues of the bioherbicides macrocidin A (1) and Z (2) with structural variance in the size of the macrocycle, its para- or meta-cyclophane character, and its functional groups were synthesized on two modular routes and tested for herbicidal, antibiotic, and antibiofilm activities. Apart from the lead compounds 1 and 2, the structurally simplified dihydromacrocidin Z (3) and normacrocidin Z (4) showed high herbicidal activity in either thistles, dandelions or in both. The derivatives 2, 3, and dibromide 9 also inhibited the growth of Staphylococcus aureus biofilms by ca 70% when applied at subtoxic concentrations as low as ca 20 µM, which are unlikely to induce bacterial resistance. They also led to the dispersion of preformed biofilms of S. aureus, exceeding a similar effect by microporenic acid A, a known biofilm inhibitor. Compounds 3 and 9 showed no noticeable cytotoxicity against human cancer and endothelial cells at concentrations below 50 µM, making them conceivable candidates for application as anti-biofilm agents in a medicinal context.

A series of 26 novel 1-(7-chloroquinolin-4-yl)-4-nitro-1H-pyrazoles bearing a dichloromethyl and an amino or thio moiety at C3 and C5 has been prepared in yields up to 72% from the reaction of 1,1-bisazolyl-, 1-azolyl-1-amino-, and 1-thioperchloro-2-nitrobuta-1,3-dienes with 7-chloro-4-hydrazinylquinoline. A new way for the formation of a pyrazole cycle from 3-methyl-2-(2,3,3-trichloro-1-nitroallylidene)oxazolidine (6) is also described. In addition, the antimalarial activity of the synthesized compounds has been evaluated in vitro against the protozoan malaria parasite Plasmodium falciparum. Notably, the 7-chloro-4-(5-(dichloromethyl)-4-nitro-3-(1H-1,2,4-triazol-1-yl)-1H-pyrazol-1-yl)quinoline (3b) and 7-chloro-4-(3-((4-chlorophenyl)thio)-5-(dichloromethyl)-4-nitro-1H-pyrazol-1-yl)quinoline (9e) inhibited the growth of the chloroquine-sensitive Plasmodium falciparum strain 3D7 with EC50 values of 0.2 ± 0.1 µM (85 ng/mL, 200 nM) and 0.2 ± 0.04 µM (100 ng/mL, 200 nM), respectively. Two compounds (3b and 10d) have also been tested for anti-SARS-CoV-2, antibacterial, and cytotoxic activity.

Edible mushrooms have been appreciated globally for their organoleptic, nutritional and chemical properties. In the present study, fruiting body of Calocybe gambosa, wild growing in Serbia, has been chemically characterized (content of macronutrients, soluble sugars, tocopherols, fatty and organic acids) and its bioactive (antimicrobial and antioxidant) properties were evaluated. The results obtained suggest that this mushroom is a source of carbohydrates and proteins (72 g/100 g dry weight (dw) and 16 g/100 g dw, respectively), with a low fat content (1.5 g/100 g dw). Sugar analysis revealed the presence of trehalose (3.82 g/100 g dw) and mannitol (0.22 g/100 g dw). Tocopherol composition revealed the presence of α-tocopherol (7.8 μg/100 g dw), while fatty acid analysis revealed the presence of 24 fatty acids with the prevalence of polyunsaturated fatty acids. Amongst organic acids, oxalic, quinic, malic, citric and fumaric acid were detected (2.8 g/100 g dw, 1.45 g/100 g dw, 11.3 g/100 g dw, 1.3 g/100 g dw, 0.08 g/100 g dw, respectively). Comprehensive antioxidant activity analysis (reducing power, DPPH radical scavenging activity, β-carotene/linoleate and TBARS assays) indicate that the mushroom is a perspective antioxidant source, whereas its antimicrobial potential turned out to be moderate. Nevertheless, at a sub--inhibitory level, the methanolic extract disrupted cell-to-cell communication using Pseudomonas aeruginosa PAO1 as a model system. Finally, enrichment of oatmeal cookies with C. gambosa flakes not only improved their nutritional value, but was praised among the participants in sensory evaluation test, indicating that along with results of chemical composition and biological activity, this mushroom has a potential to be regarded as functional food.