Early Reduction of SARS-CoV-2 Replication in Bronchial Epithelium by Kinin B2 Receptor Antagonism

Background: SARS-CoV2 has evolved to enter the host via the ACE2 receptor which is part of the Kinin-kallirein pathway. This complex pathway is only poorly understood in context of immune regulation but critical to control infection. This study examines SARS-CoV2 infection and epithelial mechanisms of the kinin-kallikrein system at the kinin B2 receptor level in SARS-CoV-2 infection that is of direct translational relevance. Methods: From acute SARS-CoV-2-positive patients and -negative controls, transcriptomes of nasal brushings were analyzed. Primary airway epithelial cells (NHBEs) were infected with SARS-CoV-2 and treated with the approved B2R antagonist icatibant. SARS-CoV-2 RNA RT-qPCR, cytotoxicity assays, plaque assays and transcriptome analyses were performed. The treatment effect was further studied in a murine airway inflammation model in vivo. Results: Here, we report a broad and strong upregulation of kallikreins and the kinin B2 receptor (B2R) in the nasal mucosa of acutely symptomatic SARS-CoV-2-positive patients. A B2R antagonist impeded SARS-CoV-2 replication and spread in NHBEs, as determined in plaque assays on Vero E6 cells. B2R antagonism reduced the expression of SARS-CoV-2 entry receptor ACE2 in vitro and in a murine airway inflammation model in vivo. In addition, it suppressed gene expression broadly, particularly genes involved in G-protein-coupled-receptor signaling and ion transport. Conclusions: In summary, this study provides evidence that treatment with B2R antagonists protects airway epithelial cells from SARS-CoV-2 by inhibiting its replication and spread, through the reduction of ACE2 levels and the interference with several cellular signaling processes. Future clinical studies need to shed light on the airway protection potential of approved B2R antagonists, like icatibant, in the treatment of early-stage COVID-19.

Unraveling the Bioactive Profile, Antioxidant and DNA Damage Protection Potential of Rye (Secale cereale) Flour

Six different solvents were used as extraction medium (water, methanol, ethanol, acidified methanol, benzene and acetone) to check their phenolics extraction efficacy from flour of two rye cultivars. Rye extracts with different solvents were further analyzed for the estimation of phytochemicals and antioxidant properties. Different tests (TPC, TAC, DPPH, FRAP, ABTS, RPA and CTC) were performed to check the antioxidant properties and tannin contents in extracts. A bioactive profile of a rye cultivar indicated the presence of total phenolic compounds (0.08–2.62 mg GAE/g), total antioxidant capacity (0.9–6.8 mg AAE/g) and condensed tannin content (4.24–9.28 mg CE/100 g). HPLC was done to check phenolics in rye extract with the best solvent (water), which indicated the presence of Catechol (91.1–120.4 mg/100 g), resorcinol (52–70.3 mg/100 g), vanillin (1.3–5.5 mg/100 g), ferulic acid (1.4–1.5 mg/100 g), quercetin (4.6–4.67 mg/100 g) and benzoic acid (5.3 mg/100 g) in rye extracts. The presence of DNA damage protection potential in rye extracts indicates its medicinal importance. Rye flour could be utilized in the preparation of antioxidant-rich health-benefiting food products.

Dynamic Tests on Polyurea-Based Hybrid Composites for Ballistic Protection

Due to its chemical and mechanical properties, polyurea gains more and more interest in military applications. In this study, polyurea and carbon nanotubes were processed as coating polymer composites for ballistic plates and/or packages, in order to increase their protection potential, meanwhile maintaining an appropriate weight and an economic accessibility. In this respect, the composite material was layered on various commercially-available materials and various thicknesses and further, the performances of the products obtained were tested in order to assess their behavior against traumas produced by shockwave, blunt, shooting and fragment.

Predicted Impact of the Viral Mutational Landscape on the Cytotoxic Response against SARS-CoV-2

The massive assessment of immune evasion due to viral mutations that potentially increase COVID-19 susceptibility can be computationally facilitated. The adaptive cytotoxic T response is critical during primary infection and the generation of long-term protection. Potential epitopes in the SARS-CoV-2 proteome were predicted for 2,915 human alleles of 71 HLA class I families. Allele families showed extreme differences in number of recognized epitopes, underscoring genetic variability of protective capacity between humans. Up to 1,222 epitopes were associated with any of the twelve supertypes, that is, allele clusters covering 90% population. Among them, the B27 supertype showed the lowest number of epitopes. Epitope escape mutations identified in ~118,000 NCBI isolates mainly involved non-conservative substitutions at the second and C-terminal position of the ligand core, or total ligand removal by large recurrent deletions. Escape mutations affected 47% of supertype epitopes, which in 21% of cases concerned isolates from two or more sub-continental areas. Some of these changes were coupled, but never surpassed 15% evaded epitopes for the same supertype in the same isolate, except for B27, which reached up to 33%. In contrast to most supertypes, eight particular allele families mostly contained alleles with few SARS-CoV-2 ligands. Isolates harboring cytotoxic escape mutations for these families co-existed geographically within sub-Saharan and Asian populations enriched in these alleles. Collectively, these data indicate that independent escape mutation events have already occurred for half of HLA class I supertype epitopes. However, it is presently unlikely that, overall, it poses a threat to the global population. In contrast, single and double mutations for susceptible alleles may be associated with viral selective pressure and alarming local outbreaks. This study highlights the automated integration of genomic, geographical and immunoinformatic information for surveillance of SARS-CoV-2 variants potentially affecting the population as a whole, as well as minority subpopulations.

Antibacterial, antioxidant, and sun protection potential of selected ethno medicinal plants used for skin infections in Uganda

Background Rural populations in Uganda rely heavily on medicinal plants for the treatment of bacterial skin infections. However, the efficacy of these medicinal plants for their pharmacological action is not known. The study aimed at evaluating the antibacterial, antioxidant, and sun protection potential of Spermacoce princeae, Psorospermum febrifugum, Plectranthus caespitosus, and Erlangea tomentosa extracts. Methods The plant samples were extracted by maceration sequentially using hexane, dichloromethane, ethyl acetate, methanol, and distilled water. Antibacterial activity of each extract was carried out using an agar well diffusion assay against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonie, Streptococcus pyogenes, and Salmonella typhi. Acute dermal toxicity of the aqueous extract of S. princeae and P. febrifugum, and E. tomentosa was assessed in young adult healthy Wistar albino rats at a dose of 8000 and 10,000 mg/kg body weight. The antioxidant activity of each extract was carried out using a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. The sun protection factor was determined using Shimadzu UltraViolet-Visible double beam spectrophotometer between 290 and 320 nm. Results The plant extracts showed good antibacterial activity against the tested bacterial strains with minimum inhibitory concentration (MIC) ranging between 3.12 and 12.5 mg/ml. There was no significant change in the levels of creatinine, alanine aminotransferase, and aspartate aminotransferase in the rats even at a higher dose of 10,000 mg/kg, which was related to the results of biochemical analysis of the blood samples from the treated and control groups. The aqueous and methanol extracts of S. princeae showed potential antioxidant properties, with half maximal inhibitory concentration (IC50) values of 59.82 and 61.20 μg/ml respectively. The organic and aqueous extracts of P. caespitosus showed high levels of protection against Ultraviolet light with sun protection potential values ranging between 30.67 and 37.84. Conclusions The study demonstrated that the selected medicinal plants possessed good antibacterial, antioxidant, and sun protection properties. Therefore, the plants are alternative sources of antibacterial, antioxidant, and sun protection agents in managing bacterial skin infections.

Microenvironment evolution and SCC behavior of subsea pipeline within disbonded coating crevice in a seawater environment under cathodic protection

Purpose This paper aims to make clear the sensitive zone of subsea pipeline to stress corrosion cracking (SCC) under a disbonded coating. Design/methodology/approach The change of microenvironment under a disbonded coating in artificial seawater was analyzed by using a rectangular crevice cell. The SCC behavior of subsea pipeline was studied by slow strain rate tensile tests. Findings The microenvironment at the crevice bottom exhibits obvious acidification, Cl- aggregation and cathodic protection potential (CP) rise. Accordingly, the susceptibility of X70 steels to SCC is high due to the intensive anodic dissolution effect. At the opening, hydrogen atom can access into the steel and induce hydrogen embrittlement effect on account of the applied over-protected CP potential, resulting in a relatively high susceptibility to SCC. The corrosiveness of the microenvironment at crevice middle, however, is mild with proper CP potential; thus, the susceptibility of X70 steel to SCC here is lower than that obtained at the opening and the crevice bottom. Originality/value A rectangular crevice cell is built to survey the microenvironment evolution under a disbonded coating in situ. The sensitive zone of subsea pipeline to SCC under a disbonded coating is clarified.

Genetic characterization of a mild isolate of papaya ringspot virus type-P (PRSV-P) and assessment of its cross-protection potential under greenhouse and field conditions

A mild isolate of Papaya ringspot virus type-P, abbreviated as PRSV-mild, from Ecuador was sequenced and characterized. The most distinguishing symptom induced by PRSV-mild was gray powder-like leaf patches radiating from secondary veins. In greenhouse experiments, PRSV-mild did not confer durable protection against a severe isolate of the virus (PRSV-sev), obtained from the same field. Furthermore, isolate specific detection in mixed-infected plants showed that PRSV-sev becomes dominant in infections, rendering PRSV-mild undetectable at 90–120 days post superinfection. Virus testing using isolate-specific primers detected PRSV-mild in two out of five surveyed provinces, with 10% and 48% of incidence in Santo Domingo and Los Ríos, respectively. Comparative genomics showed that PRSV-mild lacks two amino acids from the coat protein region, whereas amino acid determinants for asymptomatic phenotypes were not identified. Recombination events were not predicted in the genomes of the Ecuadorean isolates. Phylogenetic analyses placed both PRSV-mild and PRSV-sev in a clade that includes an additional PRSV isolate from Ecuador and others from South America.