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.

Mutational analysis of exon 8 and exon 14 of ATP7B gene in Bangladeshi children with Wilson disease.

BACKGROUND : Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the Adenosine Triphosphate 7B (ATP7B) gene. The spectrum of ATP7B mutation varies in different populations. The objective of this study was to identify the mutation in exon 8 and exon 14 of ATP7B gene in Bangladeshi children clinically diagnosed as WD. We also aimed to explore the phenotypic presentation. METHODS: It was a cross sectional observational study. The study was conducted at the Department of Paediatric Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2017 to June 2018. A total of 37 patients diagnosed with WD were enrolled for the study. Venous blood (about 3 mL) was drawn aseptically from each patient into tube containing ethyline diamine tetraacetic acid (EDTA) and preserved at -30°C for long-term preservation. The peripheral blood leukocytes of the patients and genomic DNAs were extracted. Exons 14 and 8 of ATP7B and their associated splice-site junctions were amplified by the polymerase chain reaction (PCR). The size and quantity of PCR products were verified by electrophoresis in 1.5% (w/v) agarose gel. 74 (37 × 2) PCR products were sent for Sanger Sequencing. The sequences were analyzed by Chromas version 2.6.6 software and the nucleotide blast was done by National Center for Biotechnology Information (NCBI) nucleoblast. Finally, the sequences were analyzed using AB Applied Bio systems and were matched with the reference sequences using MEGA software. RESULTS: In this study, a single novel homozygous mutation pLeu.1071Val in the exon 14 was found in every (100%) studied child clinically diagnosed with WD. Heterozygous mutation p.Gly1061Glu in exon14 was also found in 6 patients (11%) with WD, which is one of the common mutations in this disease. In exon 8, p.Arg778Leu mutation was detected in one patient (2.7%), which is common in the Chinese and the South Asian populations and was heterozygous. Two novel heterozygous missense mutations p.K785R (2.7%) and p.S744F (2.7%) were also found in two other children in the exon 8. CONCLUSION: We found three novel mutations in Bangladeshi children with WD, one of which may be tagged as founder mutation for Bangladeshi population. This finding indicates the necessity to study the mutation profiles of the whole ATP7B gene in our population for risk prediction. A further large-scale study will help in the development of a Mutational Data Base of Bangladeshi population with WD.

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.

Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties.

Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand.

Transition Metal Complexes of Naproxen: Synthesis, Characterization, Forced Degradation Studies, and Analytical Method Verification.

The aim of our current research was to synthesize some transition metal complexes of Naproxen, determine their physical properties, and examine their relative stability under various conditions. Characterizations of these complexes were done by 1H-NMR, Differential Scanning Calorimetry (DSC), FT-IR, HPLC, and scanning electron microscope (SEM). Complexes were subjected to acidic, basic, and aqueous hydrolysis as well as oxidation, reduction, and thermal degradation. Also the reversed phase high-performance liquid chromatography (RP-HPLC) method of Naproxen outlined in USP was verified for the Naproxen-metal complexes, with respect to accuracy, precision, solution stability, robustness, and system suitability. The melting points of the complexes were higher than that of the parent drug molecule suggesting their thermal stability. In forced degradation study, complexes were found more stable than the Naproxen itself in all conditions: acidic, basic, oxidation, and reduction media. All the HPLC verification parameters were found within the acceptable value. Therefore, it can be concluded from the study that the metal complexes of Naproxen can be more stable drug entity and offer better efficacy and longer shelf life than the parent Naproxen.