ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Synergistic antimicrobial effect of lactocin AL705 and nisin combined with organic acid salts against Listeria innocua 7 in broth and a hard cheese

The effectiveness of antimicrobial mixtures against Listeria innocua 7, used as a L. monocytogenes surrogate, was investigated in broth and a food system. Synergistic effects were found for nisin (Nis), potassium sorbate (PS), calcium propionate (CP) and sodium lactate (SL), Nis + PS being the most effective binary mixture that exhibited listericidal activity in broth. To assess the effect of adding lactocin AL705 (AL705) to Nis + organic acid salt combinations, tridimensional isobolograms were generated. Sub-MIC combinations of the antimicrobials exerted bactericidal activity against L. innocua 7 after AL705 addition to the binary mixtures. However, when applied on Sardo cheese contaminated with L. innocua 7 (initial inoculum 4.45 ± 0.06 CFU g⁻¹), only Nis + PS + AL705 produced count reductions respect to the control, reaching 3.04 ± 0.35 CFU g⁻¹ counts after 15 days at 15 °C. Ternary combinations containing AL705 showed potential to reduce antimicrobial usages for L. innocua 7 inhibition.     

Influence of Cu<Superscript>2+</Superscript> ions on structural and magnetic properties of NiZn ferrites

The paper is devoted to the preparation of NiZn ferrite with small substitutions of copper by means of ceramic technology. The influence of small Cu substitution on the microstructural and magnetic properties of NiZn ferrites have been analysed by means of various experimental methods and interpreted from the point of view of preparation technology optimisation and possible applications of such materials. A strong correlation between the substituent content and resulting properties has been observed, thus allowing preparation of material with the properties tailored for any particular application.     

Comparison between the LLC-MK2 and MDCK cell lines in the isolation of parainfluenza virus from nasopharyngeal aspirates

BACKGROUND: We report a prospective comparative study of the efficacy of three commercial cell lines in the isolation of the parainfluenza (PI) virus from nasopharyngeal samples. MATERIAL AND METHODS: In a 16 months period we studied all nasopharyngeal samples from patients with the suspension of a viral respiratory infection. The compared cell lines were LLC-MK2 and MDCK. All samples were processed by the shell-vial assay, incubated 3 days at 36 degrees C. The monolayers were stained by an indirect immunofluorescence assay with a monoclonal antibody against the nucleoprotein of the PI virus. RESULTS: In the study period 746 samples were analyzed, 46 PI virus were isolated, all belonged to the serotype 3. The LLC-MK2 cell line isolated 44 viruses (95.6%) and the MDCK cell line 41 (89.1%), no statistically significant differences were detected (p = 0.14) (qualitative sensitivity). In 84.8% of positive samples, the PI virus was isolated simultaneously in the two cell lines. Neither cell line isolated all PI virus. No statistical differences were detected in the quantitative sensitivity, although the LLC-MK2 cell line detected a slightly more samples with a low viral load (70.4 vs 68.2%). CONCLUSIONS: In view of the results obtained in this study, we believe that anyone of the two cell lines would be used in the isolation of the PI virus from respiratory samples.     

Laser Induced Periodic Structures on Polymer Surfaces

Subhalf micron (0.2 nm) space and amplitude linear periodic structures and an array of dot images are obtained with the Nd:YAG laser irradiation on Kapton polyimide films, poly(ethylene terephthalate) films, spin-coated polyimide films and others. Different from the excimer laser irradiation, which requires a polarizer, our solid state Nd:YAG laser source provides polarized beams without a polarizer with advantage over excimer laser irradiation. AFM and SEM studies have been carried out. XPS studies of laser exposed areas indicate no significant chemical reactions took place on exposed areas.     

Interaction of protein percent with caloric density and protein source for lactating cows

Experiment 1 was to test effect of three ratios of energy to protein in complete mixed diets for 36 lactating cows in three, 28-d periods. Energy was varied with cottonseed hulls, pelleted ground corrugated boxes, and a mixture of the two. Crude protein was varied with soybean meal to give energy:crude protein of 5.7, 5.0, and 4.6 for each energy amount. Cottonseed meal was compared with soybean meal in corrugated box diets. Feed intake was much higher with cottonseed hulls, and appreciable feedlot bloat resulted from pelleted ground corrugated box diets. Data adjusted to equal feed intake showed significant effect of energy to crude protein ratio on milk yield and improved digestion of organic matter with soybean meal vs. cottonseed meal. Experiment 2 tested the hypothesis that lactating cows consuming high-protein alfalfa may benefit from supplemental protein. Diets were 50% forage. Six diets were 14 or 18% crude protein in three ratios of alfalfa hay to corn silage (0:100, 50:50, 100:0). Additional corn silage diets were to compare: 14 versus 18% protein from distiller's dried grains with solubles only and with .5 or .9% urea (four diets); two 14% protein diets compared .6% added potassium chloride with or without .5% urea. Thirty-six Holstein cows in early lactation received one of the 12 diets in each of three 28-d periods. Distiller's grains with solubles markedly depressed milk yield (2.2 kg/d) and milk protein (.22%); heat damage of distiller's grains was evident. Protein interacted with alfalfa so gain in milk from 18 versus 14% increased from .55 to 1.36 to 2.66 kg/d as alfalfa changed from 0 to 50 to 100%. Thus, crude protein of alfalfa was not as effective as that from soybean meal in supporting milk yield.     

The molecular biology of bladder carcinoma

OBJECTIVE: The clinical course of transitional cell carcinoma of the bladder can be difficult to predict due to its potential to invade the muscle layer and/or develop to a high grade lesion. Bladder carcinoma can arise from genetic changes that may activate the oncogenes (-c-erbB2, c-erbB1, c-myc, ras, etc.) and/or inactivate the suppressor genes (p53, Rb). The aim of the present study is to continue a study protocol on the molecular biology of bladder tumors. METHODS/RESULTS: From January, 1993 to January, 1995, 85 patients were studied. These patients were divided into two groups: the first group comprised 14 controls of urothelial tissue and the second comprised 65 cases of transitional cell carcinoma of the bladder. p53 expression was determined by an immunohistochemical method (NCL-p53-DO7 monoclonal antibody). Quantification of the p8 oncoprotein in cytosol and EGFR (epidermal growth factor receptor) in membrane was performed by ELISA (Oncogene Science) and RIA (Vienna Lab), respectively. A statistically significant relationship between the expression of p53 and EGFR with tumor stage and grade was found. Quantification of p185 and EGFR showed higher values in the tumor tissue than in the control samples, but a worse survival could not be determined. CONCLUSIONS: The present study shows that p53 expression can be considered to be a prognostic factor. It provides useful information on the aggressive behaviour of the tumor and has a direct relation with the survival rates.