In silico pharmacology最新文献

{"title":"Effect of bioactive compounds of <i>Mucuna pruriens</i> on proteins of Wnt/β catenin pathway in pulmonary hypertension by in silico approach.","authors":"Supriya Bhosle, Shrilaxmi Bagali, Prachi P Parvatikar, Kusal K Das","doi":"10.1007/s40203-024-00263-8","DOIUrl":"10.1007/s40203-024-00263-8","url":null,"abstract":"<p><p>Modulation of the Wnt/β-catenin signaling pathway may aid in discovering new medications for the effective management of pulmonary artery hypertension (PAH). Given the therapeutic potential of Mucuna pruriens in several diseases, the present study aimed to analyze interactions of different bioactive compounds of Mucuna pruriens plant seeds with Wnt/β-catenin pathway targeting its various components like Wnt 3a, Frizzled 1, LRP 5/6, β-catenin, Disheveled, cyclin D1 by in silico analysis. The proposed work is based on computational analysis including ADME/T properties, by a Swiss ADME server. To understand the molecular interaction pattern Schrodinger, suit a stand-alone software was used to predict the interaction of bioactive molecules of <i>Mucuna Pruriens</i> with target proteins that are involved in Wnt/ β catenin pathway. Further, the simulation pattern of the top docked complex was subjected to MD simulation in Desmond for 100 ns. Bioactive molecules from Mucuna Pruriens have drug-like properties and minimal toxicity. Further, the docking study revealed that among the nine compounds, three compounds (Gallic acid, L-dopa, and β-sitosterol) showed good interaction with target proteins. As gallic acid showed good interaction with all target proteins, the docked complex was subjected to MD simulation which was stable throughout the simulation time in terms of RMSD and RMSF. These findings suggest that the bioactive molecules of <i>Mucuna pruriens</i> compounds have potential therapeutic value in the treatment of pulmonary vascular disease. Further, in vivo and in vitro studies are necessary to determine its efficacy and validate its pharmacological activity conclusively.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"110"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico study of novel dimeric flavonoid (OC251FR2) isolated from the seeds of <i>Garcinia kola</i> Heckel (<i>Clusiaceae</i>) against alpha estrogen receptor (ER-α) of breast cancer.","authors":"Tunmise T Eugene-Osoikhia, Nnenna W Odozi, Emmanuel O Yeye, Mohammed Isiaka, Ibrahim A Oladosu","doi":"10.1007/s40203-024-00282-5","DOIUrl":"10.1007/s40203-024-00282-5","url":null,"abstract":"<p><p>Estrogen hormone dependence accounts for a major cause in the incidence of women breast cancer. ER-<i>α</i> is the major ER subtype in the mammary epithelium and plays a critical role in breast cancer progression. Tamoxifen (1-[4-(2-dimethylaminoethoxy)-phenyl]-1,2- diphenylbut-1(Z)-ene) is a nonsteroidal antiestrogen prodrug which formed pharmacologically active metabolite, 4-hydroxytamoxifen, largely used for endocrine therapy in pre and postmenopausal women with ER-positive breast cancer. However, long term treatment with tamoxifen results in acquires resistance and high probability of disease recurring, hence the need for an alternative breast cancer drug. In silico approach was used to investigate the inhibitory activities of a novel dimeric flavanonol OC251FR2 (3,3'-oxybis(5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one)-3,3'-oxybis(5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one) isolated from the chloroform fraction of <i>Garcinia kola</i>, against alpha Estrogen receptor (ER-α); a major contributor to the growth of breast cancer. The docking was conducted using Maestro module 13.5 to obtained the ER-α PDB (5W9C) from NCBI. The OC251FR2 was docked using ligprep module with 4-hydroxytamoxifen being the reference drug. The qikpro was used to investigate the drug-likeliness while ligand docking and induced fit docking were used to investigate the interaction and binding affinity of the ligands with the active sites of the PDB. The result shows that the isolated OC251FR2 with docking score value of -6.214 interact more with amino acids in the active sites via H-bond, pi-pi interaction than the reference drug 4-Hydroxytamoxifen with a docking score value of -5.289. The drug-likeliness determined by qikpro shows that OC251FR2 violated three of the Lipinski rules of 5, and also have percent oral absorption. The quantum mechanics values show that OC251FR2 have similar properties comparable to the reference drug 4-hydroxytamoxifen. Hence, can serve as potential lead against alpha Estrogen receptor (ER-α).</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00282-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"108"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytotherapeutic potential of <i>Campomanesia xanthocarpa</i> (Mart.) O. Berg: antitumor effects in vitro and in silico, with emphasis on SK-MEL-28 melanoma cells-a study on leaf and fruit infusions.","authors":"Vanessa Ruana Ferreira da Silva, Gilnei Bruno da Silva, Daiane Manica, Carolina Turnes Pasini Deolindo, Margarete Dulce Bagatini, Aniela Pinto Kempka","doi":"10.1007/s40203-024-00286-1","DOIUrl":"10.1007/s40203-024-00286-1","url":null,"abstract":"<p><p>The study investigated the efficacy of <i>Campomanesia xanthocarpa</i> infusions on human melanoma cells (SK-MEL-28). The phytochemical profile revealed 18 phenolic compounds in the leaf infusion and 9 in the fruit infusion. After 24 h of treatment, the infusions demonstrated antineoplastic effects, reducing cell viability at all tested concentrations for the leaf infusion. For the fruit infusion, a significant reduction in cell viability was observed specifically at the 800 μg/mL concentration. Fluorescence microscopy and mitochondrial membrane potential results indicated that the leaf infusion was more effective in reducing cell viability and mitochondrial function in SK-MEL-28 cells, possibly due to its greater variety of phenolic compounds compared to the fruit infusion. The leaf infusion also induced higher production of intracellular reactive oxygen species compared to the fruit infusion. Protein sulfhydryl levels were reduced for the leaf infusion. Epigallocatechin gallate, Isoquercitrin, Rutin, Kaempferol-3-O-rutinoside, Chlorogenic acid, and Ellagic acid were identified as the main compounds with activity against SK-MEL-28 cells. Molecular docking analysis underscored factors such as affinity, cavity size, binding mode, and contact residues with specific compounds chosen for their favorable properties in targeting BRAF, CDK4, CDK6, MEK1, and MEK2. The variability in binding affinities may directly influence the compounds' ability to inhibit different signaling pathways related to cancer cell growth and proliferation. The results suggest that phenolic compounds from <i>C. xanthocarpa</i> extracts have therapeutic potential and could contribute to melanoma therapies.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00286-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"105"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSAR, molecular docking, MD simulations, and ADMET screening identify potential <i>Heliotropium indicum</i> leads against key targets in benign prostatic hyperplasia.","authors":"Emmanuel Sunday Omirin, Precious Oluwasanmi Aribisala, Ezekiel Abiola Olugbogi, Olawole Yakubu Adeniran, Sunday Adeola Emaleku, John Ayodeji Saliu, Oluwaseun Fapohunda, Abimbola Kikelomo Omirin, Mary Oyinlola Gbadamosi, Iheanyichukwu Wopara","doi":"10.1007/s40203-024-00280-7","DOIUrl":"10.1007/s40203-024-00280-7","url":null,"abstract":"<p><p>Steroid 5α-reductase (5αR) converts testosterone into dihydrotestosterone (DHT), a potent androgen driving prostate cell proliferation via the androgen receptor (AR). Both 5αR and AR play crucial roles in androgen-mediated disorders, making them key therapeutic targets in drug development. Current treatments target these enzymes individually and often cause significant side effects, highlighting the need for safer alternatives. Through <i>in silico</i> screening, 13 pyrrolizidine alkaloids of <i>Heliotropium indicum</i> (HI) were assessed for their inhibitory potential against 5αR and AR. Using machine learning, six alkaloids showed promising pIC50 values. The accuracy of the models was assessed using key statistical parameters, including the score, correlation coefficient for training sets (R²), correlation coefficient for test sets (Q²), standard deviation (SD), and root mean square error (RMSE). For 5αR, the results were 0.763 (R²), 0.781 (Q²), 0.748 (score), 0.362 (SD), and 0.832 (RMSE), while for AR, the values were 0.817 (R²), 0.783 (Q²), 0.713 (score), 0.427 (SD), and 0.782 (RMSE), indicating reliability. Europine-N-oxide (-10.27 kcal/mol) and Heliotridine-N-oxide (-9.72 kcal/mol) displayed stronger 5αR binding than Finasteride, while Heliotrine (-10.09 kcal/mol) and Europine-N-oxide (-8.76 kcal/mol) outperformed Enzalutamide in AR binding. Key hydrogen bonds and MD simulations confirmed stable interactions. Pharmacokinetic screening revealed favorable drug-like profiles, including good solubility and absorption with minimal CYP enzyme inhibition. These findings suggest that HI alkaloids are promising multi-target inhibitors for BPH treatment, warranting further in vivo validation and optimization.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00280-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"107"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the effect of <i>1</i>,<i>2-Dibenzoylhydrazine</i> on <i>Staphylococcus aureus</i> using integrated computational approaches.","authors":"Kola A Oluwafemi, Rashidat B Jimoh, Damilola A Omoboyowa, Adebisi Olonisakin, Anthony F Adeforiti, Naveed Iqbal","doi":"10.1007/s40203-024-00278-1","DOIUrl":"https://doi.org/10.1007/s40203-024-00278-1","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i>, a notorious member of the ESKAPE pathogens, poses significant public health challenges due to its virulence and multidrug-resistant nature, particularly in methicillin-resistant <i>S. aureus</i> (MRSA) strains. With the increasing threat of antibiotic resistance, there is an urgent need to develop novel antibiotic agents. This study therefore aims to explore the antibacterial potential of <i>1</i>,<i>2</i>-dibenzoylhydrazine (DBH) as a scaffold against <i>S. aureus</i> drug target enzymes, using integrated computational approaches. The study utilized molecular docking, lead optimization, and structure-based virtual screening techniques to evaluate the binding affinities of DBH and its derivatives against various <i>S. aureus</i> enzymes. Prime/MM-GBSA calculations were performed to validate the binding affinities obtained, and molecular dynamics (MD) simulations were conducted to assess the stability of the DBHs-enzyme complexes. Results indicated that, out of twenty enzymes from <i>S. aureus</i> examined against DBH, carotenoid dehydrosqualene synthase was predicted as a suitable target enzyme for DBH, showing a binding affinity of -8.027 kcal/mol. A lead optimization operation of the compound generated 27 DBH derivatives out of which four exhibited enhanced binding affinities compared to both DBH and a standard antibiotic, ofloxacin. The QSAR model predicted that, DBH and molecule_D_1 have higher PIC₅₀ of 4.779 µM compared with the standard drug (ofloxacin = 4.678 µM). MD simulations confirmed the stability of the top-scoring derivatives within the enzyme's binding pocket, with RMSD and RMSF analyses supporting their potential as inhibitors of the enzyme. In conclusion, this study has predicted the effect of DBH derivatives on <i>S. aureus</i> based on their in silico inhibitory capacity against the carotenoid dehydrosqualene synthase from the organism. Future work will seek to experimentally validate these findings against the suggested enzyme.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00278-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"102"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperidin's role in the treatment of lung cancer: <i>In-silico</i> and <i>In-vitro</i> findings.","authors":"Swati Arora, Sumit Sheoran, Bhuvanesh Baniya, Naidu Subbarao, Himanshu Singh, Dhamodharan Prabhu, Neeraj Kumar, Smita C Pawar, Sugunakar Vuree","doi":"10.1007/s40203-024-00265-6","DOIUrl":"https://doi.org/10.1007/s40203-024-00265-6","url":null,"abstract":"<p><p>Lung Cancer remains a significant health concern, necessitating the exploration of novel therapeutic avenues due to the limited efficacy and adverse effects of current treatments. In this study, we utilized a thorough <i>in-silico</i> and <i>in-vitro</i> methodology to develop prospective drugs for the treatment of lung cancer. The active components of <i>Citrus latifolia</i> were identified through the utilization of a variety of pharmacological instruments, such as Gene Ontology, GeneCards, DrugBank, the Chinese Traditional Drug Database, and GeneMANIA. Subsequent molecular docking studies using GOLD software revealed Hesperidin as the most promising candidate, exhibiting a remarkable binding affinity (GOLD score: 60.98 kcal/mol) towards the epidermal growth factor receptor (EGFR), a pivotal target in lung cancer therapy. Further validation through Schrodinger-Glide redocking reaffirmed the robust interaction between Hesperidin and EGFR. Pharmacokinetic profiling of top-scoring ligands indicated favorable drug-like properties, supporting their therapeutic potential. Molecular dynamics simulations employing Desmond software demonstrated the structural stability and persistence of the Hesperidin-EGFR complex over a 100-ns trajectory, corroborating its efficacy. Additionally, cytotoxicity analysis revealed a potent inhibitory effect of Hesperidin with an IC₅₀ value of 34.25 µg/ml. Collectively, our findings underscore Hesperidin from <i>Citrus latifolia</i> as a promising candidate for lung cancer therapy, warranting further investigation through <i>in-vivo</i> studies for clinical translation.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"104"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico molecular interaction analysis of phytochemicals extracted from <i>Ornithogalum narbonense</i> flowers.","authors":"Erdi Can Aytar, Emine İncilay Torunoğlu, Betül Aydın, Alper Durmaz","doi":"10.1007/s40203-024-00272-7","DOIUrl":"https://doi.org/10.1007/s40203-024-00272-7","url":null,"abstract":"<p><p>This study used various assays to analyse the antioxidant activity and phenolic content of <i>Ornithogalum narbonense</i> flowers. The DPPH radical scavenging activity was found to have an IC₅₀ value of 1276.00 µg/mL, the iron chelating activity was 5.12 mg/mL, and the total flavonoid content was 33.14 mg QE/g extract ± 4.76. Gas chromatography analysis identified various bioactive compounds, with ethane, 1,1-diethoxy- being the most dominant at 52.87% of the total area. Molecular docking studies revealed that 3,5-Di-tert-butylphenol and 9-Octadecene exhibit significant binding affinity with human ferritin L chain (2FFX), suggesting their potential to influence iron chelation activity. Toxicity evaluations showed LD50 values of 800 mg/kg for 3,5-Di-tert-butylphenol and 2760 mg/kg for 9-Octadecene, categorising them into toxicity classes 4 and 5. Both compounds demonstrated minimal activity across various toxicity models. However, they displayed specific interaction profiles with targets such as Prostaglandin G/H Synthase 1 and Amine Oxidase A. In-silico cytotoxicity predictions highlighted the potential anticancer activity of 3,5-Di-tert-butylphenol against Hs 683 oligodendroglioma cells and 9-Octadecene against A2058 melanoma cells. These findings emphasise the anticancer potential of <i>O. narbonense</i> phytochemicals and the significance of molecular docking and toxicity profiling in drug discovery.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"103"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering phosphodiesterase-5 inhibitors from <i>Aframemum melegueta</i>: computational models against erectile dysfunction.","authors":"Damilola Alex Omoboyowa","doi":"10.1007/s40203-024-00284-3","DOIUrl":"https://doi.org/10.1007/s40203-024-00284-3","url":null,"abstract":"<p><p>Insufficient and inability to maintain erection in male for satisfactory sexual performance remains global challenge among couples. The identification of phosphodiesterase-5 (PDE-5) antagonist in the pathogenesis of erectile dysfunction has improved the search for therapeutic agents for the management of this sexual dysfunction. Here in, bioactive compounds from <i>Aframomum melegueta</i> were virtually screened against PDE-5 using Schrodinger suite 2017-1 as computational tool. The lead compound was further validated in comparison with sildenafil by performing 100 ns molecular dynamics (MD) simulation using Desmond. Among 109 bioactive compounds screened, nine (9) molecules were predicted as potent inhibitors of PDE-5 with binding affinities comparable to the co-crystalized ligand (sildenafil). 1,7-bis(3,4-dihyroxy-5-methoxyphenyl)heptane-3,5-diyldiacetate was observed to have the best docking score (-11.522 kcal/mol) among the hit compounds which is very close to the co-crystalized ligand (-11.872 kcal/mol). Validation using pharmacophore hypothesis and QSAR modeling further confirmed the prediction of the hit compounds with fitness score ranging from 0.754 to 2.605 and predicted pIC50 of 3.835 to 7.976 µM. All the hit compounds obeyed Lipinski's rule of five and within the reference range of the pharmacokinetics parameters. The MD simulation result predicted the stability of 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyldiacetate-PDE-5 complex comparable to the sildenafil-PDE-5 complex. The outcome of this study predicted nine molecules from <i>A. melegueta</i> as potent PDE-5 antagonists which required isolation and experimental validation for the management of erectile dysfunction.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00284-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"101"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Multiple-Epitope-Based Vaccine for Hepatitis C Virus Genotypes 1a and 1b: an in-silico reverse vaccinology approach.","authors":"Enakshi Das, Mahesh Samantaray, Kajal Abrol, Jayarani Basumatari, Shilpa Sri Pushan, Amutha Ramaswamy","doi":"10.1007/s40203-024-00275-4","DOIUrl":"https://doi.org/10.1007/s40203-024-00275-4","url":null,"abstract":"<p><p>The Hepatitis C virus (HCV) is a blood-transmitted virus responsible for persistent inflammation, presenting a substantial worldwide health challenge. HCV, characterized by a positive-stranded ribonucleic acid genome, possesses an intricate genetic makeup encoding both structural and non-structural proteins, crucial for sustaining its life cycle. The Direct Acting Antivirals have revolutionized the treatment landscape of HCV promoting higher Sustained Virological Response rates. Despite significant advancements in treatment, no vaccines are currently available against HCV. The development of effective HCV vaccines becomes challenging as the genetic diversity of HCV virus and its complex nature of the immune response required for protection. In this work, the immunoinformatics methods were utilized to develop a multiple-epitope-based vaccine towards an effective treatment against the viral HCV polyprotein. The vaccine was constructed by T-cell epitopes extracted from the viral polyprotein of HCV genotypes 1a and 1b. The vaccine was highly antigenic, non-toxic, and non-allergenic. Effective binding of the designed vaccine construct was studied by forming complexes with the human immune Toll-Like Receptors; TLR3 and TLR8. The MD simulation of these receptor-vaccine complexes were performed for 50ns and the immunological simulation of modeled vaccine in presence of receptors for 365 days timeline validated the stability of the constructed vaccine. The in-silico vaccine construct developed from this work might be beneficial as prophylactic measures against the HCV variants, if explored further in in vivo and in vitro methods. Consequently, this research outcome is presumed to have implications in the development of safer and more efficient vaccines for lethal diseases.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00275-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"100"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaffold transforming and in-silico design of potential androgen receptor antagonists in prostate cancer therapy.","authors":"Ajay Kumar Gupta, Piyush Ghode, Sanmati Kumar Jain","doi":"10.1007/s40203-024-00274-5","DOIUrl":"https://doi.org/10.1007/s40203-024-00274-5","url":null,"abstract":"<p><p>Androgens like testosterone and dihydrotestosterone are essential for the growth and development of the prostate gland. Androgenic receptors are overexpressed, which promotes the progression of prostate cancer; therefore, androgenic receptors are a key target in the therapy of prostate cancer. Enzalutamide is used to treat prostate cancer; however, it also causes toxicities such as cardiovascular toxicity, acute myocarditis, hypertension, and seizures. The objective of this research was to create novel and safer analogues of enzalutamide, followed by the prediction of the pharmacokinetic and toxicity characteristics of these enzalutamide analogues. Molecular docking studies of analogues were also done to guess how ligands will work biologically in treating prostate cancer. A total of 195 analogues were generated, and among them, 23 bioisosteres were selected for further pharmacokinetic, toxicological screening and docking studies. The predicted physical-chemical, medicinal, and ADMET characteristics of the designed bioisosteres were optimal to good compared to enzalutamide. Additionally, the drug likeness and drug score of analogues were superior to enzalutamide. According to docking studies of analogues, EZ12, EZ8, and EZ10 formed hydrogen bonds of SER778 with replaceable amide groups in enzalutamide molecules. SER778 residue may be responsible for antagonistic activity towards androgen receptors. Based on the results of the ADMET, drug likeness, drug score, and docking study of designed enzalutamide analogues, the ligands EZ12, EZ8, and EZ10 could be used to find more possible antiandrogen drugs that could be used to treat prostate cancer.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"99"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}