Identification of Leading Compounds from Euphorbia neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies.

Coronavirus disease-19 (COVID-19) are deadly and infectious disease that impacts individuals in a variety of ways. Scientists have stepped up their attempts to find an antiviral drug that targets the spike protein (S) of Angiotensin converting enzyme 2 (ACE2) (receptor protein) as a viable therapeutic target for coronavirus. The most recent study examines the potential antagonistic effects of 17 phytochemicals present in the plant extraction of Euphorbia neriifolia on the anti-SARS-CoV-2 ACE2 protein. Computational techniques like molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations, and molecular dynamics (MD) simulation analysis were used to investigate the actions of these phytochemicals. The results of molecular docking studies showed that the control ligand (2-acetamido-2-deoxy-ß-D-glucopyranose) had a binding potential of -6.2 kcal/mol, but the binding potentials of delphin, ß-amyrin, and tulipanin are greater at -10.4, 10.0, and -9.6 kcal/mol. To verify their drug-likeness, the discovered hits were put via Lipinski filters and ADMET analysis. According to MD simulations of the complex run for 100 numbers, delphin binds to the SARS-CoV-2 ACE2 receptor's active region with good stability. In root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) calculations, delphinan, ß-amyrin, and tulipanin showed reduced variance with the receptor binding domain subunit 1(RBD S1) ACE2 protein complex. The solvent accessible surface area (SASA), radius of gyration (Rg), molecular surface area (MolSA), and polar surface area (PSA) validation results for these three compounds were likewise encouraging. The convenient binding energies across the 100 numbers binding period were discovered by using molecular mechanics of generalized born and surface (MM/GBSA) to estimate the ligand-binding free energies to the protein receptor. All things considered, the information points to a greater likelihood of chemicals found in Euphorbia neriifolia binding to the SARS-CoV-2 ACE2 active site. To determine these lead compounds' anti-SARS-CoV-2 potential, in vitro and in vivo studies should be conducted. How to cite this article: Islam MN, Pramanik MEA, Hossain MA, et al. Identification of Leading Compounds from Euphorbia Neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies. Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.

Euphorbia neriifolia Leaf Juice on Mild and Moderate COVID-19 Patients: Implications in OMICRON Era.

Coronavirus disease-2019 (COVID-19) has shattered the public health delivery system of most of the countries of the world. COVID-19 displays variable clinical presentations. The severe COVID-19 represents a fulminant pathological condition and most of the patients run a downhill course if extensive medical measures are not adopted. The major challenges about COVID-19 are related to develop strategies to manage huge populations of mild and moderate cases of COVID-19 with two realistic purposes: (1) early negativity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and (2) arrest of progression of moderate COVID-19 patients from developing severe complications. Although several medications have been repurposed for these purposes, none of these have passed the test of time in global perspective. Thus, there remains a pressing need to develop new and novel innovative management strategies for these patients as new variants of SARS-CoV-2 have been destroying the normal public health delivery system of different countries from time to time. The study presented here has checked the safety and efficacy of a herbal medication, leaves of Euphorbia neriifolia Linn (E. neriifolia), in mild and moderate COVID-19 patients. Sixty patients (30 mild COVID-19 and 30 moderate COVID-19) were enrolled in the study. Fifteen mild COVID-19 patients received standard of care (SOC) management, and the remaining 15 patients received SOC plus E. neriifolia. The moderate COVID-19 patients similarly received either SOC (N = 15) or SOC plus E. neriifolia (N = 15). Although there were marked diversity regarding biochemical parameters of these patients at entry, the moderate COVID-19 patients receiving E. neriifolia showed decrease in C-reactive protein and D-dimer and increase in oxygen saturation 7 days after trial commencement. However, these improvements were not detected in moderate COVID-19 patients receiving SOC. Hospital staying was significantly lower in both mild and moderate COVID-19 patients receiving SOC plus E. neriifolia than those receiving only SOC. Taken together, it may be proposed that usage of E. neriifolia may have beneficial effects regarding management for COVID-19 patients, especially for those in developing and resource-constrained countries, although a conclusive statement may not be given due to small sample size. This herbal medication is also pertinent in the context of emergence of OMICRON variant of COVID-19 as the overload of SARS-CoV-2-infecetd patients may be addressed considerably by this medication without hospitalization, if proper communication between patients and physicians can be ensured. How to cite this article: Pramanik MEA, Miah MMZ, Ahmed I, et al. Euphorbia neriifolia Leaf Juice on Mild and Moderate COVID-19 Patients: Implications in OMICRON Era. Euroasian J Hepato-Gastroenterol 2022;12(1):10-18.

Plasma Kynurenine to Tryptophan Ratio Is Not Associated with Undernutrition in Adults but Reduced after Nutrition Intervention: Results from a Community-Based Study in Bangladesh.

Infections and persistent immunological activation are linked to increased kynurenine (KYN) and the KYN-to-Tryptophan (TRP) or KT ratio and may be critical factors in undernutrition. We sought to determine the association between the KT ratio and adult malnutrition, as well as investigate if nutritional supplementation had any influence on the decrease of the KT ratio. A total of 525 undernourished adults aged 18-45 years were recruited and provided a nutrition intervention for 60 feeding days. TRP and KYN concentrations were determined from plasma samples using LC-MS/MS. At baseline, the median (interquartile range (IQR)) TRP, KYN and KT ratios were 24.1 (17.6, 34.3) µmol/L, 0.76 (0.53, 1.18) µmol/L and 30.9 (24.5, 41.7), respectively. Following intervention, the median (IQR) KYN and KT ratios were significantly reduced to 0.713 (0.46, 1.12) µmol/L and 27.5 (21.3, 35.8). The KT ratio was found to be inversely linked with adult BMI (coefficient: -0.09; 95% CI: -0.18, 0.004; p-value = 0.06) but not statistically significant. Additionally, Plasma CRP was correlated positively, while LRP1 was inversely correlated with the KT ratio. Our data suggest that in Bangladeshi adults, the KT ratio is not related to the pathophysiology of malnutrition but correlated with inflammatory and anti-inflammatory biomarkers, and the ratio can be reduced by a nutrition intervention.

Plasma Kynurenine to Tryptophan Ratio Is Negatively Associated with Linear Growth of Children Living in a Slum of Bangladesh: Results from a Community-Based Intervention Study.

Chronic exposure to infectious agents results in environmental enteric dysfunction-a significant contributor to childhood stunting. Low plasma tryptophan (TRP), increased kynurenine (KYN), and KYN-TRP (KT) ratio are associated with infections and chronic immune activation. We postulated that both these conditions are interlinked, and therefore aimed to identify the association between KT ratio and the linear growth of Bangladeshi children. A total of 480 stunted and at risk of being stunted children aged 12-18 months were enrolled and provided nutrition intervention for 90 days. Plasma samples were assessed using liquid chromatography tandem mass spectrometry to measure TRP and KYN concentrations. Multivariable linear regression with generalized estimating equations was applied to analyze association between the KT ratio and linear growth. Tryptophan, KYN, and KT ratio were significantly higher in stunted children than in children at risk of being stunted both at baseline and at the end of nutrition intervention. Following intervention, the median (interquartile range [IQR]) KYN concentration was significantly reduced from 4.6 (3.6, 5.4) µmol/L to 3.9 (0.3, 7.6) µmol/L, and median (IQR) KT ratio decreased from 104 (80.9, 131) to 92.8 (6.6, 247) in stunted children. We also found KT ratio to be negatively associated (coefficient = -0.7; 95% CI = -1.13, -0.26; P-value = 0.002) with linear growth. In addition, KYN and KT ratio were positively correlated with fecal neopterin and plasma C-reactive protein, whereas TRP was negatively correlated with both of these biomarkers and alpha-1-acid glycoprotein. Our findings imply that KT ratio is associated in the pathophysiology of stunting as well as with biomarkers of inflammation in Bangladeshi children.

Bacteriophages Isolated from Stunted Children Can Regulate Gut Bacterial Communities in an Age-Specific Manner.

Stunting, a severe and multigenerational growth impairment, globally affects 22% of children under the age of 5 years. Stunted children have altered gut bacterial communities with higher proportions of Proteobacteria, a phylum with several known human pathogens. Despite the links between an altered gut microbiota and stunting, the role of bacteriophages, highly abundant bacterial viruses, is unknown. Here, we describe the gut bacterial and bacteriophage communities of Bangladeshi stunted children younger than 38 months. We show that these children harbor distinct gut bacteriophages relative to their non-stunted counterparts. In vitro, these gut bacteriophages are infectious and can regulate bacterial abundance and composition in an age-specific manner, highlighting their possible role in the pathophysiology of child stunting. Specifically, Proteobacteria from non-stunted children increased in the presence of phages from younger stunted children, suggesting that phages could contribute to the bacterial community changes observed in child stunting.