PubChem Database Research Articles

Evaluation of mechanical features and antibacterial potential of fluoroquinolone against β-ketoacyl-ACP synthases (FabB, FabF & FabH) via computational approaches

The synthesis of fatty acids, which are essential for the growth and survival of bacterial cells, is catalyzed by beta-keto acyl-ACP synthase I-III. Due to the significant differences between the bacterial ACP synthase enzyme and the mammalian enzyme, it may serve as a viable target for the development of potent anti-bacterial medications. In this study, a sophisticated molecular docking strategy was employed to target all three KAS enzymes. Initially, 1000 fluoroquinolone derivatives were obtained from PubChem database, along with the commonly used ciprofloxacin, and subjected to virtual screening against FabH, FabB, and FabF, respectively. Subsequently, molecular dynamics (MD) simulations were conducted to confirm the stability and reliability of the generated conformations. The compounds 155813629, 142486676, and 155567217 were found to exhibit potential molecular interactions against FabH, FabB, and FabF, respectively, with docking scores of −9.9, −8.9, and −9.9 kcal/mol. These scores outperformed the docking score of standard ciprofloxacin. Furthermore, MD simulations were used to assess the dynamic nature of molecular interactions in both physiological and dynamic settings. Throughout the simulated trajectory, all three complexes displayed favorable stability patterns. The findings of this investigation suggest that fluoroquinolone derivatives may serve as highly effective and selective inhibitors of the KAS enzyme.

Cananga odorata (Ylang-Ylang) modulate pathways involved in cancer: Gene set enrichment and network pharmacology approach

Traditionally, Cananga odorata Hook. F. & Thomson (Ylang-Ylang) is commonly used to treat various diseases and has been assessed for anti-cancer potency in experimental animal models. However, the affinity of its phytocompounds with multiple proteins involved in the pathogenesis of cancer has not been illuminated yet. The present study was framed to elucidate the molecular mechanisms of Cananga odorata for its anticancer activity via compound-gene set pathway enrichment analysis, network pharmacology, and docking studies. Initially, phytocompounds were retrieved from herbs databases and literature. Structural information of each compound was obtained from the PubChem database. Druggable characteristics and side effects were predicted using MolSoft and ADVERpred. ADMET profile was predicted using PreADMET online server. Possible target proteins of each compound were predicted by BindingDB (p≥0.7). Compounds modulating the target proteins associated with the cancer were separated based on the successful and approved targets available in the Therapeutic Target Database. STRING and KEGG pathway database was used to analyze the molecular pathways modulated by the protein targets. The interaction between compounds, proteins, and pathways was constructed by Cytoscape 3.6.1, and docking of compounds with protein target was performed using AutoDock 4.2. Among 26 compounds, 12 phytocompounds were identified to modulate 34 pathways associated with cancer. 4-hydroxy-5,6,7-trimethoxyflavanone and Reticuline showed the maximum interactions with proteins involved in cancer. All 12 compounds obeyed the rule of five and p-methoxybenzaldehyde scored the highest drug-likeness score. Micheline A and Anonaine showed the highest binding affinity with Ubiquitin-protein ligase E3 (MDM2). The current study provides the molecular documentation of phytocompounds from Cananga odorata in the regulation of multi-proteins and pathways associated with progression of cancer (mainly Gastric, Melanoma, Prostate, and Breast cancer), which can be further investigated via wet-lab protocols.

A computational study to identify Sesamol derivatives as NRF2 activator for protection against drug-induced liver injury (DILI).

Drug-induced liver injury can be caused by any drugs, their metabolites, or natural products due to the inefficient functioning of drug-metabolizing enzymes, resulting in reactive oxygen species generation and leading to oxidative stress-induced cell death. For protection against oxidative stress, our cell has various defense mechanisms. One of the mechanisms is NRF2 pathway, when activated, protects the cell against oxidative stress. Natural antioxidants such as Sesamol have reported pharmacological activity (hepatoprotective & cardioprotective) and signaling pathways (NRF2 & CREM) altering potential. A Computational analysis was done using molecular docking, IFD, ADMET, MM-GBSA, and Molecular dynamic simulation of the Schrödinger suite. A total of 63,345 Sesamol derivatives were downloaded for the PubChem database. The protein structure of KEAP1-NRF2 (PDB: 4L7D) was downloaded from the RCSB protein database. The molecular docking technique was used to screen compounds that can form an interaction similar to the co-crystalized ligand (1VX). Based on MM-GBSA, docking score, and interactions, ten compounds were selected for ADMET profiling and IFD. After IFD, five compounds (66867225, 46148111, 12444939, 123892179, & 94817569) were selected for molecular dynamics simulation (MDS). Protein-ligand complex stability was assessed during MDS. The selected compounds (66867225, 46148111, 12444939, 123892179, & 94817569) complex with KEAP1 protein shows good stability and bond retentions. In our study, we observed that the selected compounds show good interaction, PCA, Rg, binding free energy, and ADMET profile. We can conclude that the selected compounds can act as NRF2 activators, which should be validated using proper in-vivo/in-vitro models.

Mechanism of andrographis paniculata on lung cancer by network pharmacology and molecular docking.

Traditional Chinese medicine (TCM) has been widely recognized and accepted worldwide to provide favorable therapeutic effects for cancer patients. As Andrographis paniculata has an anti-tumor effect, it might inhibit lung cancer. The drug targets and related pathways involved in the action of Andrographis paniculata against lung cancer were predicted using network pharmacology, and its mechanism was further explored at the molecular level. This work selected the effective components and targets of Andrographis paniculata against the Traditional Chinese Medicine System Pharmacology (TCMSP) database. Targets related to lung cancer were searched for in the GEO database (accession number GSE136043). The volcanic and thermal maps of differential expression genes were produced using the software R. Then, the target genes were analyzed by GO and KEGG analysis using the software R. This also utilized the AutoDock tool to study the molecular docking of the active component structures downloaded from the PubChem database and the key target structures downloaded from the PDB database, and the docking results were visualized using the software PyMol. The results of molecular docking show that wogonin, Mono-O-methylwightin, Deoxycamptothecine, andrographidine F_qt, Quercetin tetramethyl (3',4',5,7) ether, 14-deoxyandrographolide, andrographolide-19-β-D-glucoside_qt and 14-deoxy-11-oxo-andrographolide were potential active components, while AKT1, MAPK14, RELA and NCOA1 were key targets. This study showed the main candidate components, targets, and pathways involved in the action of Andrographis paniculata against lung cancer.

Structure-based computational design of novel covalent binders for the treatment of sickle cell disease

The quest in finding an everlasting panacea to the pernicious impact of sickle cell disease (SCD) in the society hit a turn of success since the recent discovery of a small molecule reversible covalent inhibitor, Voxelotor. A drug that primarily promotes the stability of oxygenated hemoglobin and inhibit the polymerization of HbS by enhancing hemoglobin's affinity for oxygen has opened a new frontier in drug discovery and development. Despite eminent efforts made to reproduce small molecules with better therapeutic targets, none has been successful. To this end, we employed the use of structure-based computational techniques with emphasis on the electrophilic warhead group of Voxelotor to harness novel covalent binders that could elicit better therapeutic response against HbS. The PubChem database and DataWarrior software were used to design random molecules using Voxelotor's electrophilic functionality. Following the compilation of these chemical entities, a high-throughput covalent docking-based virtual screening campaign was conducted which revealed three (Compound_166, Compound_2301, and Compound_2335) putative druglike candidates with higher baseline energy value compared to the standard drug. Subsequently, in silico ADMET profiling was carried out to evaluate their pharmacokinetics and pharmacodynamics properties, and their stability was evaluated for 1 μs (1 μs) using molecular dynamics simulation. Finally, to prioritize these compounds for further development in drug discovery, MM/PBSA calculations was employed to evaluate their molecular interactions and solvation energy within the HbS protein. Despite the admirable druglike and stability properties of these compounds, further experimental validations are required to establish their preclinical relevance for drug development.

Role of death-associated protein kinase 1 (DAPK1) in retinal degenerative diseases: an in-silico approach towards therapeutic intervention

The Death-associated protein kinase 1 (DAPK1) has emerged as a crucial player in the pathogenesis of degenerative diseases. As a serine/threonine kinase family member, DAPK1 regulates critical signaling pathways, such as apoptosis and autophagy. In this study, we comprehensively analyzed DAPK1 interactors and enriched molecular functions, biological processes, phenotypic expression, disease associations, and aging signatures to elucidate the molecular networks of DAPK1. Furthermore, we employed a structure-based virtual screening approach using the PubChem database, which enabled the identification of potential bioactive compounds capable of inhibiting DAPK1, including caspase inhibitors and synthetic analogs. Three selected compounds, CID24602687, CID8843795, and CID110869998, exhibited high docking affinity and selectivity towards DAPK1, which were further investigated using molecular dynamics simulations to understand their binding patterns. Our findings establish a connection between DAPK1 and retinal degenerative diseases and highlight the potential of these selected compounds for the development of novel therapeutic strategies. This study provides valuable insights into the molecular mechanisms underlying DAPK1-related diseases, and offers new opportunities for the discovery of effective treatments for retinal degeneration. Communicated by Ramaswamy H. Sarma

Network Pharmacology to Investigate the Mechanism of Ginseng and Atractylodis Macrocephalae to Prevent Diarrhea

To investigate the molecular mechanism of Ginseng and Atractylodes macrocephala in the prevention and treatment of diarrhea based on network pharmacology and molecular docking. The active ingredients and the related targets of Ginseng and Atractylodes were searched and collected through TCMSP database, PubChem database and Swiss TargetPrediction. With the help of GeneCards database, OMIM database and DisGeNET database, we searched for disease related targets with "Diarrhea" as the keyword, and the obtained targets of drug ingredients were intersected with the disease targets to obtain the results. The predicted targets of Ginseng and Atractylodes for diarrhea were obtained by intersection. Cytoscape 3.9.1 software was used to construct the "drug-active ingredient-target network" diagram. Protein interaction information was obtained by using String database, and the target network was further analyzed by CytoNCA plug-in to screen the core targets. The core targets were enriched by KEGG pathway analysis using the microbiology platform, and the results were based on the enrichment results. The KEGG enrichment analysis showed that the core targets acted on PI3K-Akt signaling pathwa, Human T-cell leukemia virus 1 ntection, Kaposi sarcoma- associated herpesvirus intection, Measles, Proteoglyeans in cancer, and 10 other pathways. Through the network pharmacology study, Ginseng and Atractylodesan regulated diarrhea involving 127 targets and 10 pathways, indicating that Ginseng and Atractylodesan can exert its effects on diarrhea prevention and treatment through multiple components, targets and pathways.

Screening potential inhibitor from actinomycetes for Dihydrofolate reductase of Staphylococcus aureus – In vitro and in silico studies

Cellulitis is a skin disease which is caused by the pathogen Staphylococcus aureus. The protein Dihydrofolate reductase is an important drug based target for Trimethoprim. Dihydrofolate reductase is reversibly inhibited by the drug trimethoprim. One of the major enzymes responsible for converting dihydrofolic acid into tetrahydrofolic acid. The screening of microbial natural products, Soil isolation is a rich source of actinomycetes. The actinomycetes sp. KK21-2 strain isolated from the soil, the aqueous extract of the isolates yielded 33 active metabolites from the LC-MS analysis. Based on the ADMETox analysis, 8 compounds were excluded and finally 25 compounds were selected for the docking analysis. Protein structure of S. aureus retrieved from PDB, drug and compounds were obtained from the PubChem Database. Molecular docking (XP) and Induced Fit Docking (IFD) were completed utilizing the Glide Module of Schrodinger. Molecular dynamics simulation employing the Schrodinger Desmond module was used to examine the stability of the docked complex. From the results of docking analysis and MD Simulation result 5-(3,4-Dihydroxy-1,5-cyclohexadien-1-yl) phenylhydantoin have suggest this compound have multi- targeting potency against the cellulitis skin disease from the pathogen Staphylococcus aureus, in future need to be verified through in vitro and in vivo analysis.

In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Main Protease among a PubChem Database of Avian Infectious Bronchitis Virus 3CLPro Inhibitors.

Remarkable structural homologies between the main proteases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the avian infectious bronchitis virus (IBV) were revealed by comparative amino-acid sequence and 3D structural alignment. Assessing whether reported IBV 3CLPro inhibitors could also interact with SARS-CoV-2 has been undertaken in silico using a PubChem BioAssay database of 388 compounds active on the avian infectious bronchitis virus 3C-like protease. Docking studies of this database on the SARS-CoV-2 protease resulted in the identification of four covalent inhibitors targeting the catalytic cysteine residue and five non-covalent inhibitors for which the binding was further investigated by molecular dynamics (MD) simulations. Predictive ADMET calculations on the nine compounds suggest promising pharmacokinetic properties.

An In Silico Molecular Modelling-Based Prediction of Potential Keap1 Inhibitors from Hemidesmus indicus (L.) R.Br. against Oxidative-Stress-Induced Diseases.

The present study investigated the antioxidant potential of aqueous methanolic extracts of Hemidesmus indicus (L.) R.Br., followed by a pharmacoinformatics-based screening of novel Keap1 protein inhibitors. Initially, the antioxidant potential of this plant extract was assessed via antioxidant assays (DPPH, ABTS radical scavenging, and FRAP). Furthermore, 69 phytocompounds in total were derived from this plant using the IMPPAT database, and their three-dimensional structures were obtained from the PubChem database. The chosen 69 phytocompounds were docked against the Kelch-Neh2 complex protein (PDB entry ID: 2flu, resolution 1.50 Å) along with the standard drug (CPUY192018). H. indicus (L.) R.Br. extract (100 µg × mL-1) showed 85 ± 2.917%, 78.783 ± 0.24% of DPPH, ABTS radicals scavenging activity, and 161 ± 4 μg × mol (Fe (II)) g-1 ferric ion reducing power. The three top-scored hits, namely Hemidescine (-11.30 Kcal × mol-1), Beta-Amyrin (-10.00 Kcal × mol-1), and Quercetin (-9.80 Kcal × mol-1), were selected based on their binding affinities. MD simulation studies showed that all the protein-ligand complexes (Keap1-HEM, Keap1-BET, and Keap1-QUE) were highly stable during the entire simulation period, compared with the standard CPUY192018-Keap1 complex. Based on these findings, the three top-scored phytocompounds may be used as significant and safe Keap1 inhibitors, and could potentially be used for the treatment of oxidative-stress-induced health complications.

Hydroxycoumarins and some Flavonoids from Pistacia atlantica Desf. as Multi-targets Inhibitors for Alzheimer's Disease: Molecular Docking and ADMET Studies.

The present study aimed to identify new selective inhibitors for acetylcholinesterase, butyrylcholinesterase, monoacylglycerol lipase, beta-secretase, and Asparagine endopeptidase, the targets enzymes in Alzheimer's disease. The inhibitory effect of P. atlantica Desf. methanol extracts against AChE were determined using Ellman's method. The molecular docking study is achieved using Autodock Vina. The structures of the molecules 3-methoxycarpachromene, masticadienonic acid, 7-ethoxycoumarin, 3',5,7- trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol-3-O-rutinoside and the five enzymes were obtained from the PubChem database and Protein databank. ADMET parameters were checked to confirm their pharmacokinetics using swiss-ADME and ADMET-SAR servers. P. atlantica Desf. methanol extracts showed a notable inhibitory effect against AChE (IC50 = 0.26 ± 0.004 mg/ml). The molecular docking results of 3-methoxycarpachromene, masticadienonic acid, 7-ethoxycoumarin, 3',5,7-trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol-3-Orutinoside with the five enzymes show significant affinities of these molecules towards Alzheimer disease targets, where they could form several interactions, such as hydrogen bonds and hydrophobic interactions with the studied enzymes. The shortest hydrogen bond is 1.7 A° between masticadienonic acid and Arg128 of the active site of BACE, while the lowest free energy is -11.2 of the complex 5,6,7,4'-tetrahydroxyflavonol-3-O-rutinoside -HuBchE. To the best of our knowledge, these molecules' potential anti-Alzheimer disease effect is studied in this paper for the first time. The docking studies of this work show that 3-methoxycarpachromene and masticadienonic acid, 7-ethoxycoumarin, 3',5,7-Trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol- 3-O-rutinoside have good affinities towards the enzymes involved in Alzheimer pathology, which confirm the ability of these molecules to inhibit the studied enzymes namely: HuAChE, HuBChE, BACE, MAGL, and AEP. These molecules might become drug candidates to prevent Alzheimer's disease.

Network pharmacology-based prediction of efficacy and mechanism of Chongmyunggongjin-dan acting on Alzheimer’s disease

Objectives: Network pharmacology is a method of constructing and analyzing a drug-compound-target network to predict potential efficacy and mechanisms related to drug targets. In that large-scale analysis can be performed in a short time, it is considered a suitable tool to explore the function and role of herbal medicine. Thus, we investigated the potential functions and pathways of Chongmyunggongjin-dan (CMGJD) on Alzheimer’s disease (AD) via network pharmacology analysis.Methods: Using public databases and PubChem database, compounds of CMGJD and their target genes were collected. The putative target genes of CMGJD and known target genes of AD were compared and found the correlation. Then, the network was constructed using Cytoscape 3.9.1. and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms.Results: The result showed that total 104 compounds and 1157 related genes were gathered from CMGJD. The network consisted of 1157nodes and 10034 edges. 859 genes were interacted with AD gene set, suggesting that the effects of CMGJD are closely related to AD. Target genes of CMGJD are considerably associated with various pathways including ‘Positive regulation of chemokine production’, ‘Cellular response to toxic substance’, ‘Arachidonic acid metabolic process’, ‘PI3K-Akt signaling pathway’, ‘Metabolic pathways’, ‘IL-17 signaling pathway’ and ‘Neuroactive ligand-receptor interaction’.Conclusion: Through a network pharmacological method, CMGJD was predicted to have high relevance with AD by regulating inflammation. This study could be used as a basis for effects of CMGJD on AD.

Mechanism of the Mongolian medicine Eerdun Wurile basic formula in improving postoperative cognitive dysfunction by inhibiting apoptosis through the SIRT1/p53 signaling pathway.

The Mongolian medicine Eerdun Wurile is a commonly used Mongolian in folk medicine used to treat cerebral nervous system diseases such as cerebral hemorrhage, cerebral thrombosis, nerve injury and cognitive function, cardiovascular diseases such as hypertension and coronary heart disease. Eerdun wurile may effect anti-postoperative cognitive function. To investigate the molecular mechanism of the Mongolian medicine Eerdun Wurile Basic Formula (EWB) in improving postoperative cognitive dysfunction (POCD) based on Network pharmacology, and to confirm involvement of the SIRT1/p53 signal pathway, one of the key signal pathways, by using the POCD mouse model. Obtain compounds and disease-related targets through TCMSP, TCMID, PubChem, PharmMapper platforms, GeneCards, and OMIM databases, and screen intersection genes; Use Cytoscape software to build a "drug-ingredient-disease-target" network, and the STRING platform for protein interaction analysis.; R software was used to analyze the function of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment.; AutoDock Vina software for active components and core targets to Perform molecular docking. The POCD mouse model was prepared by intracerebroventricular injection of lipopolysaccharide (LPS), and the morphological changes of hippocampal tissue were observed by hematoxylin-eosin (HE) staining, Western blot, immunofluorescence and TUNEL were used to verify the results of network pharmacological enrichment analysis. There were 110 potential targets for improving POCD by EWB, 117 items were enriched by GO, and 113 pathways were enriched by KEGG, among which the SIRT1/p53 signaling pathway was related to the occurrence of POCD. Quercetin, kaempferol, vestitol, β-sitosterol and 7-methoxy-2-methyl isoflavone in EWB can form stable conformations with low binding energy with core target proteins IL-6, CASP3, VEGFA, EGFR and ESR1. Animal experiments showed that compared with the POCD model group, the EWB group could significantly improve the apoptosis in the hippocampus of the mice, and significantly down-regulate the expression of Acetyl-p53 protein (P<0.05). EWB can improve POCD with the characteristics of multi-component, multi-target, and multi-pathway synergistic effects. Studies have confirmed that EWB can improve the occurrence of POCD by regulating the expression of genes related to the SIRT1/p53 signal pathway, which provides a new target and basis for the treatment of POCD.

Virtual prediction of Brown Rice Gamma Oryzanol as anti-inflammation via COX-1 and COX-2 inhibitions

Brown rice gamma oryzanol (GO) is an important bioactive compound with numerous potential health functions, such as anti-inflammatory and anti-diabetic. Cyclooxygenase (COX) is the enzyme that mediates the biological transformation of arachidonic acid (ARA) into prostaglandins (PGs) in the mechanism of inflammation. This study purposed to identify the potency of gamma oryzanol of brown rice as an anti-inflammatory compound via COX-1 and COX-2 inhibition. The three-dimensional structure of COX-1 and COX-2 was determined by binding affinity calculations from virtual molecular docking with gamma oryzanol ligand through in silico study. Arachidonic acid as native ligand of COX-1/COX-2 was performed as a control in this study. Gamma oryzanol (CIS 5282164) and arachidonic acid (CIS 444899) were downloaded in 3D-SDF format from the PubChem database. The three-dimensional model of COX-1 and COX-2 was acquired from the protein data bank (www.rscb.org) in PDB format. The molecular docking was performed by Vina Wizard integrated on PyRx version 0.8. The interaction between GO and COX-1/COX-2 was visualized using the Discovery Studio version 2022 software. Molecular dynamics (MD) simulation also used to analyze the stability of the protein-ligand complex. The results showed that brown rice gamma oryzanol binds to COX-1 and COX-2 at many active sites with strongest binding affinity compared to arachidonic acid, with energy binding -7.8 kcal/mol and -6.2 kcal/mol, respectively. This in silico study concluded that brown rice gamma oryzanol has potential function as an anti-inflammatory activity through COX-1 and COX-2 catalysis reduction.

Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment.

Obesity is a pandemic and a serious health problem in developed and undeveloped countries. Activation of estrogen receptor beta (ERβ) has been shown to promote weight loss without modifying caloric intake, making it an attractive target for developing new drugs against obesity. This work aimed to predict new small molecules as potential ERβ activators. A ligand-based virtual screening of the ZINC15, PubChem, and Molport databases by substructure and similarity was carried out using the three-dimensional organization of known ligands as a reference. A molecular docking screening of FDA-approved drugs was also conducted as a repositioning strategy. Finally, selected compounds were evaluated by molecular dynamic simulations. Compounds 1 (-24.27 ± 0.34 kcal/mol), 2 (-23.33 ± 0.3 kcal/mol), and 6 (-29.55 ± 0.51 kcal/mol) showed the best stability on the active site in complex with ERβ with an RMSD < 3.3 Å. RMSF analysis showed that these compounds do not affect the fluctuation of the Cα of ERβ nor the compactness according to the radius of gyration. Finally, an in silico evaluation of ADMET showed they are safe molecules. These results suggest that new ERβ ligands could be promising molecules for obesity control.

Cyanobacterial compound Tolyporphine K as an inhibitor of Apo-PBP (penicillin-binding protein) in A. baumannii and its ADME assessment

Antibiotic-resistant Acinetobacter baumannii, is a common pathogen found in hospital settings and has become nosocomial due to its high infection-causing tendency amongst ICU patients. The present study explores the cyanocompoundswhich were capable to inhibit the Penicillin Binding Protein of A. baumannii through molecular docking, ADMET, and molecular dynamicssimulation strategy. A database having structural and origin details was generated for 85 bioactive compounds in MS Excel. The 3-D structures weredownloaded from the PubChem database and minimized. The receptor protein was minimized and validated for structure correctness. The database was screened against the penicillin-binding protein of A. baumannii through PyRx software. The top 5 compounds including the control molecule werefurther redocked to the receptor molecule through Autodock Vina software. The molecule pose having the highest affinity was further subjected to 100ns MD- simulation and simultaneously the in-vitro activity of the methanol extract and hexane extract was checked through agar well diffusion assay.Docking studies indicate Tolyporphine K to be a lead molecule which was further assessed through Molecular dynamics and MM/PBSA. The in-silicoresults suggested that the protein-ligand complex was found to be stable over the 100 ns trajectory with a binding free energy of -8.56 Kcalmol-1. Theligand did not induce any major structural conformation in the protein moiety and was largely stabilized by hydrophobic interactions. The bioactivityscore and ADME properties of the compounds were also calculated. The in-vitro agar well diffusion assay showed a moderate zone of inhibition of12.33mm. The results indicate that the compound Tolyporphin- K could be a potential inhibitor of penicillin-binding protein in A. baumannii. Yet furtherwork needs to be done to have a more concrete basis for the pathway of inhibition. Communicated by Ramaswamy H. Sarma

Novel Drug Development for Treatment of COVID-19 by In Silico Analysis: Identification of SARS-Cov-2 Inhibiting Streptomyces Compounds

In accordance with the present epidemiological paradigm, viral mutations of the virus are on the rise, and their natural effects are being selected for at a higher rate than normal. According to the World Health Organization (WHO), the global COVID-19 pandemic induced by the Delta and Omicron strain of the SARS-CoV-2 virus could propagate and disseminate more rapidly than other viruses thanks to its many mutations, and these also caused some very significant health problems. The established medications would eventually start to lose their efficacy since the variation mutated more quickly than the original stain. As protein spikes are the point of origin or epitome for the mutations to take place, it would be most effective to target the remaining vital enzymes by binding the proteins with the largest pocket sizes. The objective of the current work is to employ in-silico analysis to discover the streptomyces chemicals that suppress the SARS-CoV-2 virus as well as its mutated strains thus promoting a healthy body. Based on the drug likeness property of compounds when subjected to molecular docking, a total of 14 compounds were identified and selected from the PUBCHEM database that showed highest binding energy with the targeted Receptor Binding Domain. The compounds namely - Streptomyces tanashiensis; Thaxtomin A; Bafilomycin A1 from Streptomyces griseus and few others as mentioned further on more research would support and confirm the utilizing of these to create new medications to treat the novel SARS-CoV-2 infectious strains.

NARINGIN'S POTENTIAL AS A HEPATITIS B VIRUS REPLICATION INHIBITOR: AN IN-SILICO STUDY OF SECONDARY METABOLITE COMPOUND

Naringin is a secondary metabolite compound of the flavonoid group which is generally found in plants that are consumed and traditionally used as medicine. The aim of this study was to examine the potential of naringin as a candidate for hepatitis B virus replication inhibitor using an in-silico approach. This research uses exploratory descriptive method with molecular docking analysis was carried out using the blind docking technique. The 3D structures of naringin and reference ligands were collected from the PubChem database, and the 3D structures of target proteins were collected from the PDB database. The target protein used is the hepatitis B virus capsid protein with PDB ID: 5GMZ. Docking analysis was performed using AutoDock Vina which is integrated into PyRx. Docking results were visualized using the PyMol software and Biovia Discovery Studio 2019. The results of the analysis showed that the binding affinity of all simulation models between naringin and the HBV capsid protein ranged from -7.1 to -7.9 kcal/mol. The binding site formed between naringin and the receptor corresponds to the reference ligand, involving the same 12 amino acid residues, namely PHE 23, PRO 25, LEU 30, THR 33, TRP 102, ILE 105, SER 106, PHE 110, TYR 118, ILE 139, LEU 140, and SER 141. Based on these results, it can be concluded that the naringin compound has the same bioactivity as the reference ligand in inhibiting viral replication, so that naringin has the potential as a candidate for hepatitis B virus replication inhibitor

VIRTUAL SCREENING OF NATURAL ALPHA-GLUCOSIDASE INHIBITOR FROM ALPINIA GALANGA BIOACTIVE COMPOUNDS AS ANTI-DIABETIC CANDIDATE

Glucose toxicity become serious risk factor of type 2 diabetes mellitus. Multiple complication can be caused of the abnormal condition of glucose level in blood. Thus, managing the plasma glucose is one of the strategy to minimize the negative effects of type 2 diabetes mellitus. In this present study, we aimed to virtually evaluate the bioactive compounds from Alpinia galanga as inhibitor agent against alpha-glucosidase, which was known as carbohydrate catabolic enzyme. The 2D structure of ligands were retrieved from PubChem database (pubchem.ncbi.nlm.nih.gov/) and were evaluated based on Lipinski rule of five for ensured the druglike-ness standard, while the sequence and 3D structure of target protein, alpha-glucosidase, was retrieved from UniProt database (https://www.uniprot.org/) and was modelled through SWISS-MODEL (swissmodel.expasy.org/). All ligands used in this study then underwent optimization prior to molecular docking and analyzing procedures. According to our prediction results, we found that galangin and 1's-1'-acetoxychavicol acetate which known as bioactive compounds found in A. galanga have significant potency as inhibitor agents against the alpha-glucosidase due to its binding affinity scores and other physicochemical properties compared to the anti-diabetic drug, mignitol. Thus, from this finding, we have recent starting point to expand the potency of these bioactive compounds, especially for inhibiting the alpha-glucosidase as the novel strategy to reduce the poor prognosis of type 2 diabetes mellitus.

Integration of Network Pharmacology and Molecular Docking to Analyse the Mechanism of Action of Oregano Essential Oil in the Treatment of Bovine Mastitis.

The active components, potential targets, and mechanisms of action of oregano essential oil in the treatment of bovine mastitis disease were investigated using network pharmacology and molecular docking approaches. The TCMSP and literature databases were examined for the main compounds in oregano essential oil. Afterward, the physical, chemical, and bioavailability characteristics of the components were evaluated. The PubChem, BATMAN, PharmMapper, and Uniprot databases were utilized to predict the target genes of the major components of oregano essential oil. Via the databases of DrugBank, OMIM, GeneCards, TTD, and DisGenet, the disease targets of bovine mastitis were discovered. We analyzed common targets and built protein-protein interaction (PPI) networks using the STRING database. Key genes were analyzed, obtained, and compound-target-pathway-disease visualization networks were created using Cytoscape. For the GO function and KEGG pathway enrichment analysis, the DAVID database was utilized. Molecular docking via Autodock Tools was utilized to evaluate the reliability of the interactions between oregano essential oil and hub targets. Thymol, carvacrol, and p-cymene are the three major components found in oregano essential oil. The potential targets (TNF, TLR4, ALB, IL-1β, TLR2, IL-6, IFNG, and MyD88) were screened according to the visual network. The enrichment analysis suggested that the major signaling pathways in network pharmacology may include PI3K-Akt, MAPK, IL-17, and NF-κ B. Molecular docking analysis shows that thymol had good docking activity with TNF, IL-6, and MyD88, carvacrol had good docking activity with TNF, and p-cymene had good docking activity with ALB. This study clarified the mechanism of action of oregano essential oil in the treatment of bovine mastitis, thus providing data supporting the potential for the use of oregano essential oil in the development of new therapeutics for bovine mastitis.