Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E.

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.

Rumex vesicarius L. boosts the effectiveness of sorafenib in triple-negative breast cancer by downregulating BCl2, mTOR, and JNK, and upregulating p21 expression.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is characterized by poor prognosis, rapid progression, serious clinical behavior, an elevated risk of metastasis, and resistance to standard treatments. Traditional medicine practitioners value Rumex vesicarius L. (RMV) for a variety of reasons, including the plant's antioxidant capabilities. Our study's goals were to ascertain the efficacy of RMV alone and in combination with sorafenib (SOR) against the aggressive TNBC cell line (MDA-MB-231) and use in vitro and in silico analysis to deduce the fundamental mechanism of action. METHODS: In the current study, molecular operating environment (MOE, 2019.0102) software was used for performing molecular docking. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to determine the cytotoxicity of RMV, SOR or RMV/SOR combination against the TNBC cell line MDA-MB-231 cells. The effects of RMV, SOR, and RMV and SOR combining on mRNAs expressions of the target genes including mTOR, p21, JNK, and BCl2 were evaluated. In TNBC cells, the relative expressions of mRNAs of the genes were examined by using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In our experiments, we discovered that both RMV extracts alone and in combination with SOR considerably reduced cancer cell proliferation (IC50 = 0.83 and 0.19 µM, respectively). Additionally, the expression of the tumor suppressor gene p21 was elevated whereas the expression of the invasion and anti-apoptosis genes BCl2, mTOR, and JNK were significantly decreased after treatment with RMV and SOR. Based on in silico analysis, it was found that RMV extract contains bioactive chemicals with a high affinity for inhibiting JNK and VEGFR-2. CONCLUSION: In conclusion, in vitro and in silico investigations show that the RMV extract improves the anticancer efficiency of SOR through molecular processes involving the downregulation of mTOR, BCl2, and JNK1 and overexpression of p21 tumor suppressor gene. Finally, we suggest conducting additional in vivo investigations on RMV and its bioactive components to verify their potential in cancer therapy.

Anti-SARS-CoV-2 in vitro potential of castor oil plant (Ricinus communis) leaf extract: in-silico virtual evidence.

Ricinus communis L. is a medicinal plant that displays valuable pharmacological properties, including antioxidant, antimicrobial, analgesic, antibacterial, antiviral and anti-inflammatory properties. This study targeted to isolate and identify some constituents of R. communis leaves using ultra-performance liquid chromatography coupled with mass spectroscopy (UPLC-MS/MS) and different chromatographic techniques. In vitro anti-MERS and anti-SARS-CoV-2 activity for different fractions and for two pure isolated compounds, lupeol (RS) and ricinine (RS1) were evaluated using a plaque reduction assay with three different mechanisms and IC50 based on their cytotoxic concentration (CC50) from an MTT assay using Vero E6 cell line. Isolated phytoconstituents and remdesivir are assessed for in-silico anti-COVID-19 activity using molecular docking tools. The methylene chloride extract showed pronounced virucidal activity against SARS-CoV-2 (IC50 = 1.76 µg/ml). It was also shown that ricinine had superior potential activity against SARS-CoV-2, (IC50 = 2.5 µg/ml). Lupeol displayed the most potency against MERS, (IC50 = 5.28 µg/ml). Ricinine appeared to be the most biologically active compound. The study showed that R. communis and its isolated compounds have potential natural virucidal activity against SARS-COV-2; however, additional exploration is necessary and study for their in vivo activity.

Synergistic antiviral activity of Lactobacillus acidophilus and Glycyrrhiza glabra against Herpes Simplex-1 Virus (HSV-1) and Vesicular Stomatitis Virus (VSV): experimental and In Silico insights.

BACKGROUND: The emergence of different viral infections calls for the development of new, effective, and safe antiviral drugs. Glycyrrhiza glabra is a well-known herbal remedy possessing antiviral properties. OBJECTIVE: The objective of our research was to evaluate the effectiveness of a newly developed combination of the probiotics Lactobacillus acidophilus and G. glabra root extract against two viral models, namely the DNA virus Herpes simplex virus-1 (HSV-1) and the RNA virus Vesicular Stomatitis Virus (VSV), with regards to their antiviral properties. METHODOLOGY: To examine the antiviral impacts of various treatments, we employed the MTT assay and real-time PCR methodology. RESULTS: The findings of our study indicate that the co-administration of L. acidophilus and G. glabra resulted in a significant improvement in the survival rate of Vero cells, while also leading to a reduction in the titers of Herpes Simplex Virus Type 1 (HSV-1) and Vesicular Stomatitis Virus (VSV) in comparison to cells that were not treated. Additionally, an investigation was conducted on glycyrrhizin, the primary constituent of G. glabra extract, utilizing molecular docking techniques. The results indicated that glycyrrhizin exhibited a greater binding energy score for HSV-1 polymerase (- 22.45 kcal/mol) and VSV nucleocapsid (- 19.77 kcal/mol) in comparison to the cocrystallized ligand (- 13.31 and - 11.44 kcal/mol, respectively). CONCLUSIONS: The combination of L. acidophilus and G. glabra extract can be used to develop a new, natural antiviral agent that is safe and effective.

Green synthesized silver nanoparticles for the treatment of diabetes and the related complications of hyperlipidemia and oxidative stress in diabetic rats.

This study was conducted to compare the impact of cinnamon silver nanoparticles (C-Ag-NPs) and cinnamon aqueous extract (CAE) on the total body weight (TBW), body weight gain (BWG), blood count (BC), fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density (LDL-C) and high-density (HDL-C) lipoprotein cholesterol, liver function enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) of normal and streptozotocin (STZ) diabetic rats. The CAE was administered to rats at different doses (50.0 and 100.0 mg/kg bw), whereas the C-Ag-NPs were ingested at doses of 25.0 and 50.0 mg/kg bw for 30 days. At the end of the experiment, the administration of high or low dosages of CAE or C-Ag-NPs to diabetic rats significantly reduced the FBG, TC, TG, and LDL-C and significantly increased the HDL-C compared with the diabetic control rats. The highest dose (50.0 mg/kg bw) of the C-Ag-NPs was the most efficient at significantly reducing (P < 0.05) the levels of all the analyzed parameters compared with the CAE. However, the treated and normal rats did not show any hypoglycemic activity after ingesting the CAE or C-Ag-NPs. Such effects were associated with considerable increases in their BWG. The diabetic rats that ingested the CAE or C-Ag-NPs showed a gradual decrease in their FBG, TC, LDL, and TG levels, but they were still higher than those in the normal rats. Furthermore, the C-Ag-NPs and CAE considerably enhanced the hepatic (GPT, GOT, ALP, and GGT) and antioxidant biomarker enzyme activities (SOD, CAT, and GPx) in diabetic rats. Relative to the untreated diabetic control, the C-Ag-NPs were more effective than the CAE in the diabetic rats. The C-Ag-NPs exhibited a protective role against hyperglycemia and hyperlipidemia in the diabetic rats and modulated their liver function enzyme biomarkers and antioxidant enzyme activities more than the CAE.

Potential synergistic effect of Alhagi graecorum ethanolic extract with two conventional food preservatives against some foodborne pathogens.

The present study aims to screen the anti-bacterial activity and synergistic interaction of A. graecorum Boiss. ethanolic extract with two food preservatives against five strains of foodborne bacteria. Disk diffusion and minimum inhibitory concentration were used for anti-bacterial assay, checkerboard assay and time-kill curve were used for the combination studies. HPLC analysis and molecular docking study were performed to corroborate the in vitro results. The ethanolic extract showed anti-bacterial activity against all tested bacterial strains with inhibition zones from 7.5 to 9.3 mm and MIC values ranged between 1.2 and 1.8 mg mL-1. The combination of the ethanolic extract with Na-benzoate or Na-propionate resulted in synergistic and additive interactions against the tested bacteria with fractional inhibitory concentration index (FICI) ranges 0.31-0.63 and no antagonism was shown. Time-kill curve assay showed that the synergistic and additive combinations have inhibitory effects on the tested strains. The ethanolic extract combination with Na-benzoate or Na-propionate can be used for development new sources of food preservatives. Testing new different natural plant extracts with food preservatives will help develop new anti-bacterial agents.

Robust Antiviral Activity of Santonica Flower Extract (Artemisia cina) against Avian and Human Influenza A Viruses: In Vitro and Chemoinformatic Studies.

The evolution of drug-resistant viral strains following natural acquisition of resistance mutations is a major obstacle to antiviral therapy. Besides the improper prescription of the currently licensed anti-influenza medications, M2-blockers and neuraminidase inhibitors, to control poultry outbreaks/infections potentiates the emergence of drug-resistant influenza variants. Therefore, there is always a necessity to find out new alternatives with potent activity and high safety. Plant extracts and plant-based chemicals represent a historical antiviral resource with remarkable safety in vitro and in vivo to control the emerging and remerging health threats caused by viral infections. Herein, a panel of purified plant extracts and subsequent plant-derived chemicals were evaluated for their anti-avian influenza activity against zoonotic highly pathogenic influenza A/H5N1 virus. Interestingly, santonica flower extract (Artemisia cina) showed the most promising anti-H5N1 activity with a highly safe half-maximal cytotoxic concentration 50 (CC50 > 10 mg/mL) and inhibitory concentration 50 (IC50 of 3.42 µg/mL). To confirm the anti-influenza activity, we assessed the anti-influenza activity of the selected plant extracts against seasonal human influenza A/H1N1 virus and we found that santonica flower extract showed a robust anti-influenza activity that was comparable to the activity against influenza A/H5N1. Furthermore, the mode of action for santonica flower extract with strong inhibitory activity on the abovementioned influenza strains was elucidated, showing a virucidal effect. To go deeper about the activity of the chemometric component of the extract, the major constituent, santonin, was further selected for in vitro screening against influenza A/H5N1 (IC50 = 1.701 µg/mL) and influenza A/H1N1 (IC50 = 2.91 µg/mL). The oxygen of carbonyl functionality in the cyclohexene ring succeeded to form a hydrogen bond with the neuraminidase active site. Despite the fact that santonin revealed similarity to both reference neuraminidase inhibitors in forming hydrogen bonds with essential amino acids, it illustrated shape alignment to oseltamivir more than zanamivir according to Tanimoto algorithms. This study highlights the applicability of santonica flower extract as a promising natural antiviral against low and highly pathogenic influenza A viruses.

In Vivo and In Silico Investigation of the Anti-Obesity Effects of Lactiplantibacillus plantarum Combined with Chia Seeds, Green Tea, and Chitosan in Alleviating Hyperlipidemia and Inflammation.

The increasing prevalence of obesity has become a demanding issue in both high-income and low-income countries. Treating obesity is challenging as the treatment options have many limitations. Recently, diet modification has been commonly applied to control or prevent obesity and its risks. In this study, we investigated novel therapeutic approaches using a combination of a potential probiotic source with prebiotics. Forty-eight adult male Sprague-Dawley rats were selected and divided into seven groups (eight rats per group). The first group was fed a high-fat diet, while the second group was a negative control. The other five groups were orally administered with a probiotic, Lactiplantibacillus plantarum (L. plantarum), and potential prebiotics sources (chia seeds, green tea, and chitosan) either individually or in combination for 45 days. We collected blood samples to analyze the biochemical parameters and dissected organs, including the liver, kidney, and pancreas, to evaluate obesity-related injuries. We observed a more significant decrease in the total body weight by combining these approaches than with individual agents. Moreover, treating the obese rats with this combination decreased serum catalase, superoxide dismutase, and liver malondialdehyde levels. A histopathological examination revealed a reduction in obesity-related injuries in the liver, kidney, and pancreas. Further docking studies indicated the potential role of chia seeds and green tea components in modulating obesity and its related problems. Therefore, we suggest that the daily administration of a pre- and probiotic combination may reduce obesity and its related problems.

Bactericidal activity of some plant essential oils against Ralstonia solanacearum infection.

Potato plants and their tubers in Egypt are affected by one of the most renowned soil-borne pathogen, Ralstonia solanacearum, that caused brown rot in potato tubers and wilt in plants. There is no efficient therapeutic bactericide so; control of bacterial wilt is very rough. The study investigated three different concentrations of seven essential plant oils under in vitro and in vivo conditions as a result of their effects on Ralstonia solanacearum growth and their possibility use as potato seed pieces dressing for controlling bacterial wilt disease incidence. In vitro, anise oil at the three tested different concentrations (0.04, 0.07, and 0.14% vol/vol) was the most effective one inhibiting the growth of T4 and W9 isolates of Ralstonia solanacearum then pursued by thyme, lemongrass, and clove oils. On the other hand, rocket oil at the tested concentration was the least effective one followed by fennel oil. However, wheat germ oil was not completely effective. In vivo, experiment revealed that anise oil at the three concentrations significantly reduced disease incidence and severity in sponta and hermes potato cultivars and their effect was associated with increase of peroxidase, polyphenoloxidase, phenols and the foliar fresh weight of treated plants as well as the weight of tubers/plant followed by thyme and lemongrass oils compared to the infected untreated control. Morphological differences in bacterial cell structure have been observed using a transmission electron microscope (TEM). Anise oil at higher concentration caused of cell wall rupture and degraded cellular components.

EGYVIR: An immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2.

Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kß p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kß/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kß pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.

Evaluation of growth and nutritional value of Brassica microgreens grown under red, blue and green LEDs combinations.

Microgreens are rich functional crops with valuable nutritional elements that have health benefits when used as food supplements. Growth characterization, nutritional composition profile of 21 varieties representing five species of the Brassica genus as microgreens were assessed under light-emitting diodes (LEDs) conditions. Microgreens were grown under four different LEDs ratios (%); red:blue 80:20 and 20:80 (R80 :B20 and R20 :B80 ), or red:green:blue 70:10:20 and 20:10:70 (R70 :G10 :B20 and R20 :G10 :B70 ). Results indicated that supplemental lighting with green LEDs (R70 :G10 :B20 ) enhanced vegetative growth and morphology, while blue LEDs (R20 :B80 ) increased the mineral and vitamin contents. Interestingly, by linking the nutritional content with the growth yield to define the optimal LEDs setup, we found that the best lighting to promote the microgreen growth was the green LEDs combination (R70 :G10 :B20 ). Remarkably, under the green LEDs combination (R70 :G10 :B20 ) conditions, the microgreens of Kohlrabi purple, Cabbage red, Broccoli, Kale Tucsan, Komatsuna red, Tatsoi and Cabbage green, which can benefit human health in conditions with limited food, had the highest growth and nutritional content.

Why Do Mice Overeat High-Fat Diets? How High-Fat Diet Alters the Regulation of Daily Caloric Intake in Mice.

OBJECTIVE: Ad libitum high-fat diets (HFDs) spontaneously increase caloric intake in rodents, which correlates positively with weight gain. However, it remains unclear why rodents overeat HFDs. This paper investigated how changing the proportion of diet that came from HFDs might alter daily caloric intake in mice. METHODS: Mice were given 25%, 50%, or 90% of their daily caloric need from an HFD, along with ad libitum access to a low-fat rodent chow diet. Food intake was measured daily to determine how these HFD supplements impacted total daily caloric intake. Follow-up experiments addressed the timing of HFD feeding. RESULTS: HFD supplements did not alter total caloric intake or body weight. In a follow-up experiment, mice consumed approximately 50% of their daily caloric need from an HFD in 30 minutes during the light cycle, a time when mice do not normally consume food. CONCLUSIONS: An HFD did not disrupt regulation of total daily caloric intake, even when up to 90% of total calories came from the HFD. However, HFDs increased daily caloric intake when provided ad libitum and were readily consumed by mice outside of their normal feeding cycle. Ad libitum HFDs appear to induce overconsumption beyond the mechanisms that regulate daily caloric intake.

Potential risk factors associated with ill-thrift in buffalo calves (Bubalus bubalis) raised at smallholder farms in Egypt.

Failure to grow (ill-thrift) in calves has a negative effect on animal production and health. The present study was carried out from November, 2009 to May, 2013 to investigate the risk factors of ill-thrift in buffalo calves. A total of 344 calves at 78 smallholder farms were selected randomly. A questionnaire was designed to include managemental, nutritional and disease risk factors. Serum selenium, copper, zinc, iron, calcium, phosphorus and magnesium were measured. Data were subjected to logistic regression analysis and results were expressed as p value, odds ratio (OR) and confidence interval (CI). Fifty-five calves (15.9%) showed ill-thrift. On animal level, the final multivariate logistic regression model showed a significant association between ill-thrift and early weaning (p < 0.01; OR: 45.755; CI: 4.35-480.25), diarrhea (p < 0.05; OR: 41.315; CI: 1.710-998.0), indoor management (p < 0.05; OR: 63.56; CI: 2.701-14.96) and low serum phosphorus (p < 0.01; 292.0; CI: 5.256-16.23). On farm level, inadequate mineral supplementation (p < 0.001; OR: 18.62; CI: 3.89-88.9) and irregular use of anthelmintics (p < 0.05; OR: 7.95; CI: 1.53-41.23) were the potential factors. Clinically, ill-thrift calves were more likely to have alopecia (p < 0.01), recumbency (p < 0.01), emaciation (p < 0.001), hypothermia (p < 0.01), inappetance (p < 0.001), lacrimation (p < 0.001), hypomotile rumen (p < 0.001), and pale mucous membrane (p < 0.001). The results of the present study indicate that ill-thrift in buffalo calves could occur as a result of interaction between management errors and disease factors. Identification of the risk factors associated with ill-thrift may provide useful information, which assist to construct the suitable preventive measures.