Phenolic compounds of Theobroma cacao L. show potential against dengue RdRp protease enzyme inhibition by In-silico docking, DFT study, MD simulation and MMGBSA calculation.

BACKGROUND: Currently, there is no antiviral medication for dengue, a potentially fatal tropical infectious illness spread by two mosquito species, Aedes aegypti and Aedes albopictus. The RdRp protease of dengue virus is a potential therapeutic target. This study focused on the in silico drug discovery of RdRp protease inhibitors. METHODS: To assess the potential inhibitory activity of 29 phenolic acids from Theobroma cacao L. against DENV3-NS5 RdRp, a range of computational methods were employed. These included docking, drug-likeness analysis, ADMET prediction, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. The aim of these studies was to confirm the stability of the ligand-protein complex and the binding pose identified during the docking experiment. RESULTS: Twenty-one compounds were found to have possible inhibitory activities against DENV according to the docking data, and they had a binding affinity of ≥-37.417 kcal/mol for DENV3- enzyme as compared to the reference compound panduratin A. Additionally, the drug-likeness investigation produced four hit compounds that were subjected to ADMET screening to obtain the lead compound, catechin. Based on ELUMO, EHOMO, and band energy gap, the DFT calculations showed strong electronegetivity, favouravle global softness and chemical reactivity with considerable intra-molecular charge transfer between electron-donor to electron-acceptor groups for catechin. The MD simulation result also demonstrated favourable RMSD, RMSF, SASA and H-bonds in at the binding pocket of DENV3-NS5 RdRp for catechin as compared to panduratin A. CONCLUSION: According to the present findings, catechin showed high binding affinity and sufficient drug-like properties with the appropriate ADMET profiles. Moreover, DFT and MD studies further supported the drug-like action of catechin as a potential therapeutic candidate. Therefore, further in vitro and in vivo research on cocoa and its phytochemical catechin should be taken into consideration to develop as a potential DENV inhibitor.

Identification of ß-cycloidal-derived mono-carbonyl curcumin analogs as potential interleukin-6 inhibitor to treat wound healing through QSAR, molecular docking, MD simulation, MM-GBSA calculation.

Interleukin-6 (IL-6) is a cytokine that involved in the different phases of wound healing. It is responsible for promoting inflammation, regulating tissue repair scar formation, stimulating the production of extracellular matrix components and recruiting immune cells to the wound site. Therefore, suppressing IL-6 is beneficial for wound healing. However, no small molecules are currently available in the market against the IL-6. As a result, this research gap motivates us to find a potential inhibitor. This study aimed to investigate the wound healing potential of novel ß-cycloidal-derived mono-carbonyl curcumin analogs reported in the literature through screening a series of computational studies. The calculated pIC50 value of 18 compounds (below 10) showed that all compounds may have potential therapeutic efficacy. Molecular docking studies revealed that compound C12 (-45.6044 kcal/mol) bound most strongly in the active site of IL-6 compared to the FDA-approved drug clindamycin (-42.3223). The Molecular Dynamic (MD) simulation displayed that lead compound C12 had the highest stability in the active site of IL-6 compared to the reference drug clindamycin. Furthermore, MMGBSA results indicated that C12 (-20.28 kcal/mol) had the highest binding energy compared to clindamycin (-8.36 kcal/mol). The ADMET analysis predicted that C12 are favourable for drug candidates. This study recommended compound C12 as a lead IL-6 inhibitor for future testing and development as therapeutics for wound healing.Communicated by Ramaswamy H. Sarma.

Green synthesis of zinc oxide nano particles using Allium cepa L. waste peel extracts and its antioxidant and antibacterial activities.

Synthesis of nanoparticles through the green approach using plant and vegetable extracts has gained popularity since they are thought to be efficient and cost-effective materials. This study is designed to synthesize zinc oxide nanoparticles (ZnO-NPs) from onion waste peel extract (Allium cepa L.) via the green synthesis approach. The synthesized ZnO-NPs were characterized by utilizing the UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), Energy Dispersive X-ray (EDX), Field Emission Scanning Electron Microscopy (FE-SEM) and X-ray Powder Diffraction (XRD)techniques. The nanoparticles formation was confirmed by the UV-Vis sharp absorption spectra at 318 and 322 nm. The synthesized ZnO-NPs size and shape was revealed by the XRD and SEM respectively. Smallest nanoparticle average crystallite size was found 57.38 nm with hexagonal shape. The bioactive functional groups that are in charge of capping and stabilizing the ZnO-NPs was assured by the FTIR data. Further, prepared ZnO-NPs were used to assess their possible antioxidant and antibacterial properties. DPPH test for free radical scavenging showed potential antioxidant properties of the synthesized ZnO-NPs. The antibacterial activity were studied against three clinical strains: P. aeruginosa, E. coli, and S. aureus with the maximum zone of inhibition 13.17 mm, 22.00 mm and 12.35 mm respectively at 100 µg/mL subsequently minimum inhibitory concentration was found 50 µg/mL for P. aeruginosa, and S. aureus whereas 100 µg/mL for E. coli. Antioxidant and antibacterial activity tests appear bio-resource based ZnO-NPs from Allium cepa L. extract have effects on free radical and growth of microorganisms.Therefore, it could be a promising candidates for agricultural and food safety applications as an effective antimicrobial agent against pathogenic microorganisms and also can address future biomedical applications after complete in vivo study.

Selected phytochemicals of Momordica charantia L. as potential anti-DENV-2 through the docking, DFT and molecular dynamic simulation.

Dengue fever is now one of the major global health concerns particularly for tropical and sub-tropical countries. However, there has been no FDA approved medication to treat dengue fever. Researchers are looking into DENV NS5 RdRp protease as a potential therapeutic target for discovering effective anti-dengue agents. The aim of this study to discover dengue virus inhibitor from a set of five compounds from Momordica charantia L. using a series of in-silico approaches. The compounds were docked into the active area of the DENV-2 NS5 RdRp protease to obtain the hit compounds. The successful compounds underwent additional testing for a study on drug-likeness similarity. Our study obtained Momordicoside-I as a lead compound which was further exposed to the Cytochrome P450 (CYP450) toxicity analysis to determine the toxicity based on docking scores and drug-likeness studies. Moreover, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties for the lead compound. Moreover, the lead compound was next subjected to molecular dynamic simulation for 200 ns in order to confirm the stability of the docked complex and the binding posture discovered during docking experiment. Overall, the lead compound has demonstrated good medication like qualities, non-toxicity, and significant binding affinity towards the DENV-2 RdRp enzyme.Communicated by Ramaswamy H. Sarma.

Short-term Treatment Outcome of Patients with Acute ST-elevation Myocardial Infarction in a Tertiary Care Hospital.

Outcome of acute ST-elevation myocardial infarction patients varies time to time. The present study was intended to find out the short-term treatment outcome of the patients admitted in hospital. This descriptive study was carried out in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from 15 January 2014 to 14 July 2014. A total of 100 patients admitted with Acute ST-elevation Myocardial Infarction confirmed on the presence of the (a) Typical chest pain of acute ST-elevation Myocardial Infarction (b) Electrocardiogram (ECG) evidence of ST segment elevation in two or more contiguous leads (c) Raised cardiac marker (Troponin I) were included in the study. Patients were randomly enrolled according to the inclusion and exclusion criteria and observe for one week. Data were processed and analyzed by using computer bases software SPSS version 19.0. Descriptive statistical methods were applied for data analysis. P value was considered as statistically significant when it is less than 0.05. Short-term treatment outcome of acute ST-elevation myocardial infarction include mechanical, arrhythmic, ischemic and inflammatory sequelae, as well as left ventricular mural thrombus. In addition to these broad categories, heart failure, arrhythmia, death are other common complications of AMI. The initiation of the complications usually results in explicit sign and symptoms of the acute MI patients. Learning of the complications in the post infarction period and the clinical syndromes develop with each complication, will allow the health care worker to evaluate and manage the complication appropriately.

In silico evaluation of usnic acid derivatives to discover potential antibacterial drugs against DNA gyrase B and DNA topoisomerase IV.

Due to the rising increase in infectious diseases brought on by bacteria and anti-bacterial drug resistance, antibacterial therapy has become difficult. The majority of first-line antibiotics are no longer effective against numerous germs, posing a new hazard to global human health in the 21st century. Through the drug-likeness screening, 184 usnic acid derivatives were selected from an in-house database of 340 usnic acid compounds. The pharmacokinetics (ADMET) prediction produced fifteen hit compounds, of which the lead molecule was subsequently obtained through a molecular docking investigation. The lead compounds, labelled compound-277 and compound-276, respectively, with the substantial binding affinity towards the enzymes were obtained through further docking simulation on the DNA gyrase and DNA topoisomerase proteins. Additionally, molecular dynamic (MD) simulation was performed for 300 ns on the lead compounds in order to confirm the stability of the docked complexes and the binding pose discovered during docking tests. Due to their intriguing pharmacological characteristics, these substances may be promising therapeutic candidate for anti-bacterial medication.Communicated by Ramaswamy H. Sarma.

Identification of Pyrazole Derivatives of Usnic Acid as Novel Inhibitor of SARS-CoV-2 Main Protease Through Virtual Screening Approaches.

The infection produced by the SARS-CoV-2 virus remains a significant health crisis worldwide. The lack of specific medications for COVID-19 necessitates a concerted effort to find the much-desired therapies for this condition. The main protease (Mpro) of SARS-CoV-2 is a promising target, vital for virus replication and transcription. In this study, fifty pyrazole derivatives were tested for their pharmacokinetics and drugability, resulting in eight hit compounds. Subsequent molecular docking simulations on SARS-CoV-2 main protease afforded two lead compounds with strong affinity at the active site. Additionally, the molecular dynamics (MD) simulations of lead compounds (17 and 39), along with binding free energy calculations, were accomplished to validate the stability of the docked complexes and the binding poses achieved in docking experiments. Based on these findings, compound 17 and 39, with their favorable projected pharmacokinetics and pharmacological characteristics, are the proposed potential antiviral candidates which require further investigation to be used as anti-SARS-CoV-2 medication.

Virtual screening of bioactive anti-SARS-CoV natural products and identification of 3ß,12-diacetoxyabieta-6,8,11,13-tetraene as a potential inhibitor of SARS-CoV-2 virus and its infection related pathways by MD simulation and network pharmacology.

Since the first prevalence of COVID-19 in 2019, it still remains the most devastating pandemic throughout the world. The current research aimed to find potential natural products to inhibit the novel coronavirus and associated infection by MD simulation and network pharmacology approach. Molecular docking was performed for 39 natural products having potent anti-SARS-CoV activity. Five natural products showed high binding interaction with the viral main protease for the SARS-CoV-2 virus, where 3ß,12-diacetoxyabieta-6,8,11,13 tetraene showed stable binding in MD simulation until 100 ns. Both 3ß,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A targeted 11 common genes that are related to COVID-19 and interact with each other. Gene ontology development analysis further showed that all these 11 genes are attached to various biological processes. The KEGG pathway analysis also showed that the proteins that are targeted by 3ß,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A are associated with multiple pathways related to COVID-19 infection. Furthermore, the ADMET and MDS studies reveals 3ß,12-diacetoxyabieta-6,8,11,13 as the best-suited compound for oral drug delivery.Communicated by Ramaswamy H. Sarma.

Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors.

Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research's primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex's stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate.Communicated by Ramaswamy H. Sarma.

Adverse In-Hospital Outcome of Transradial PCI in Comparison to Transfemoral PCI in NSTEMI Patients during Index Hospitalization: A Single Center Study in Bangladesh.

NSTEMI patients, in comparison to STEMI patients, are more at risk of bleeding, access site complication and MACE after PCI during index hospitalization. Because they get, multiple adjuvant anti-thrombotic agents before PCI than do the STEMI patients undergoing primary PCI. Transradial access (TRA) is proven to decrease those adverse in-hospital outcomes compared to transfemoral access (TFA) in STEMI patients. But very few studies were conducted in this regard considering NSTEMI patients. We observed prospectively the adverse in-hospital outcomes of total 180 NSTEMI patients who had undergone PCI through TRA (Group I = 80) and TFA (Group II = 100) during index hospitalization between October 2017 to September 2018 in National Institute of Cardiovascular Disease (NICVD), Dhaka, Bangladesh. Samples were selected purposively. Patients were followed up 2 hours after PCI and thereafter every day until discharge. Demographic and risk factor variables were almost same in both groups. TRA, compared with TFA, yielded less major bleeding (0% versus 3%, p=0.12) which was statistically non-significant. Minor bleeding was significantly less in Group I (2.5% versus 13.0%, p=0.04). Overall bleeding was also significantly less in Group I (2.5% and 10.0%; p=0.002). Access site complication was non-significantly less in Group I (0% versus 1%, p=0.91). TRA caused non-significant reduction in MACE (2.5% versus 5%; p=0.38) but significant reduction of total adverse in-hospital outcome (5% versus 20%, p=0.006%). In this study TRA seems to have less adverse in-hospital outcome than TFA in NSTEMI patients undergoing PCI during index hospitalization.

Integrated Nutritional Supports for Diabetic Patients During COVID-19 Infection: A Comprehensive Review.

BACKGROUND: Diabetes mellitus is an endocrine metabolic disorder, which affects the major organs in human and comorbid with others. Besides, diabetic patients are more prone to various infectious diseases as well as COVID-19 sporadic infection which is a high risk for patients with diabetes mellitus. To combat these infections and comorbid situations, an integrated balanced nutritional supportive could help in maintaining sound health and increase immunity for prevention and management of such type of viral infections. OBJECTIVES: While information regarding nutritional supports in COVID-19 pandemic in diabetic patients is not available, this review aimed to accumulate the evidence from previous publications where studied about nutrition-based supports or interventions for viral diseases with special emphasis on respiratory infections. METHODS: For reviewing, searches are done for getting journal articles into Google Scholar, Pub Med/Medline, Database of Open Access Journal and Science Direct for relevant data and information. RESULTS: Integrated nutritional supports of both macronutrients and micronutrients guidelines, including home-based physical exercise schedule, is summarized in this comprehensive review for possible prevention and management of diabetic patients in COVID-19 infections. The immuneboosting benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections of diabetic patients are also included. CONCLUSION: There is an urgent need for a healthy diet and integrated nutritional supports with home-based physical activities for diabetic patients during the self-isolation period of COVID-19 Infection.

Mucormycosis (black fungus) in COVID-19 patients-Will it be another matter of concern in the midst of the COVID-19 flare-up in Bangladesh?

Many countries of the world have been combating the new variant of severe acute respiratory syndrome coronavirus 2. Black fungus is an opportunistic foe that may cause fatal infection in immunocompromised and steroid-treated coronavirus disease 2019 (COVID-19) patients. The COVID-19 associated mucormycosis (CAM) is now a serious concern throughout the world, including many Asian countries. Therefore, along with early and accurate diagnostic facilities, special care, and prompt, but coordinated approach are recommended to combat the CAM in patients.

Orbital competition of Mn3+ and V3+ ions in Mn1+x V2-x O4.

The structural and magnetic properties of Mn1+x V2-x O4 (0 < x ⩽ 1) have been investigated by the heat capacity, magnetization, x-ray diffraction and neutron diffraction measurements, and a phase diagram of temperature versus composition was built up. For x ⩽ 0.3, a cubic-to-tetragonal (c > a) phase transition was observed. For x > 0.3, the system maintained the tetragonal lattice. Although the collinear and noncollinear magnetic transitions of V3+ ions were obtained in all compositions, the canting angles between the V3+ ions decreased with Mn3+-doping, and the ordering of the Mn3+ ions was only observed as x > 0.4. In order to study the dynamics of the ground state, the first principles simulation was applied to analyze not only the orbital effects of Mn2+, Mn3+, and V3+ ions, but also the related exchange energies.

Collaural Sinus: A Case Report.

First branchial cleft anomalies are embryological defect account for 8-10% of all branchial cleft defects. Approximately 17% of all Paediatric cervical masses are due to branchial anomalies. Despite of the fact that these anomalies are benign, secondary infection, positional effect and complication of treatment like surgery account for morbidity. Here one such case of 30 years old lady who presented to us with one discharging sinus in the floor of the right external auditory canal with a swelling in the upper neck for about 20 years. On examination showed one discharging sinus opening in the floor of right external auditory canal (EAC) and a cystic swelling in upper neck between sternomastoid and mandible. While compression over the swelling cheesy discharge comes out from EAC. MRI showed oval shaped fluid signal intensity lesion measuring about 4 × 2.1 × 1.6cm in right infra auricular region with slit like curvilinear tract about 10mm extending from upper part of the lesion opening into the antero-inferior part of external auditory canal at the junction of bony and cartilaginous part. Histopathology report showed a cyst lined by stratified squamous epithelium; wall is composed of fibrocollagenous tissue with mucous gland. The wall is densely infiltrated with lymphocytes forming lymphoid follicles at places. This paper presents a case report of collaural sinus from Otology unit, Department of Otolaryngology-Head & Neck Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.

Microscopic evidence for Mn-induced long range magnetic ordering in MAX phase compounds.

Zero and low field nuclear magnetic resonance measurements have been performed on MAX phase samples (Cr1-x Mn x )2AC with A = Ge and Ga in order to obtain local microscopic information on the nature of magnetism in this system. Our results unambiguously provide evidence for the existence of long-range magnetic order in (Cr0.96Mn0.04)2GeC and for (Cr0.93Mn0.07)2GaC, but not for (Cr0.97Mn0.03)2GaC. We point to a possible dependence of long range magnetic order in these MAX phase compounds on the A atom.

Encephalopathies with KCNC1 variants: genotype-phenotype-functional correlations.

OBJECTIVE: To analyze clinical phenotypes associated with KCNC1 variants other than the Progressive Myoclonus Epilepsy-causing variant p.Arg320His, determine the electrophysiological functional impact of identified variants and explore genotype-phenotype-physiological correlations. METHODS: Ten cases with putative pathogenic variants in KCNC1 were studied. Variants had been identified via whole-exome sequencing or gene panel testing. Clinical phenotypic data were analyzed. To determine functional impact of variants detected in the Kv 3.1 channel encoded by KCNC1, Xenopus laevis oocyte expression system and automated two-electrode voltage clamping were used. RESULTS: Six unrelated patients had a Developmental and Epileptic Encephalopathy and a recurrent de novo variant p.Ala421Val (c.1262C > T). Functional analysis of p.Ala421Val revealed loss of function through a significant reduction in whole-cell current, but no dominant-negative effect. Three patients had a contrasting phenotype of Developmental Encephalopathy without seizures and different KCNC1 variants, all of which caused loss of function with reduced whole-cell currents. Evaluation of the variant p.Ala513Val (c.1538C > T) in the tenth case, suggested it was a variant of uncertain significance. INTERPRETATION: These are the first reported cases of Developmental and Epileptic Encephalopathy due to KCNC1 mutation. The spectrum of phenotypes associated with KCNC1 is now broadened to include not only a Progressive Myoclonus Epilepsy, but an infantile onset Developmental and Epileptic Encephalopathy, as well as Developmental Encephalopathy without seizures. Loss of function is a key feature, but definitive electrophysiological separation of these phenotypes has not yet emerged.

Homozygous TANGO2 Single Nucleotide Variants Presenting with Additional Manifestations Resembling Alternating Hemiplegia of Childhood-Expanding the Phenotype of a Recently Reported Condition.

CASE: We report a 15-year-old Indian girl born to a consanguineous couple, who presented with epilepsy, developmental delay, neuroregression, and episodes of alternating hemiparesis. In addition, she had one episode of rhabdomyolysis at the age of 7 years. Extensive genetic and metabolic work up through the years was unrevealing. Eventually a trio whole exome sequencing (WES) revealed homozygous single nucleotide variants in TANGO2 gene. DISCUSSION: TANGO2 related recurrent metabolic crises with encephalomyopathy and cardiac arrhythmias were described very recently and only 15 cases were reported in literature at the time of writing. Alternating hemiplegia of childhood which was seen in our patient, has not been described in previous patients with TANGO2 mutation, and thereby expands the emerging phenotypic spectrum of this novel entity. This report also reiterates the utility of WES in diagnosing newly recognized neurogenetic conditions.

A suite-level review of the neutron powder diffraction instruments at Oak Ridge National Laboratory.

The suite of neutron powder diffractometers at Oak Ridge National Laboratory (ORNL) utilizes the distinct characteristics of the Spallation Neutron Source and High Flux Isotope Reactor to enable the measurements of powder samples over an unparalleled regime at a single laboratory. Full refinements over large Q ranges, total scattering methods, fast measurements under changing conditions, and a wide array of sample environments are available. This article provides a brief overview of each powder instrument at ORNL and details the complementarity across the suite. Future directions for the powder suite, including upgrades and new instruments, are also discussed.