Bioinformatics and Biology Insights最新文献

{"title":"Prediction of Human Papillomavirus-Host Oncoprotein Interactions Using Deep Learning.","authors":"Sheila Santa, Samuel Kojo Kwofie, Kwasi Agyenkwa-Mawuli, Osbourne Quaye, Charles A Brown, Emmanuel A Tagoe","doi":"10.1177/11779322241304666","DOIUrl":"10.1177/11779322241304666","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) causes disease through complex interactions between viral and host proteins, with the PI3K signaling pathway playing a key role. Proteins like AKT, IQGAP1, and MMP16 are involved in HPV-related cancer development. Traditional methods for studying protein-protein interactions (PPIs) are labor-intensive and time-consuming. Computational models are becoming more popular as they are less labor-intensive and often more efficient. This study aimed to develop a deep learning model to predict interactions between HPV and host proteins.</p><p><strong>Method: </strong>To achieve this, available HPV and host protein interaction data was retrieved from the protocol of Eckhardt et al and used to train a Recurrent Neural Network algorithm. Training of the model was performed on the SPYDER (scientific python development environment) platform using python libraries; Scikit-learn, Pandas, NumPy, and TensorFlow. The data was split into training, validation, and testing sets in the ratio 7:1:2, respectively. After the training and validation, the model was then used to predict the possible interactions between HPV 31 and 18 E6 and E7, and host oncoproteins AKT, IQGAP1 and MMP16.</p><p><strong>Results: </strong>The model showed good performance, with an MCC score of 0.7937 and all other metrics above 88%. The model predicted an interaction between E6 and E7 of both HPV types with AKT, while only HPV31 E7 was shown to interact with IQGAP1 and MMP16 with confidence scores of 0.9638 and 0.5793, respectively.</p><p><strong>Conclusion: </strong>The current model strongly predicted HPVs E6 and E7 interactions with PI3K pathway, and the viral proteins may be involved in AKT activation, driving HPV-associated cancers. This model supports the robust prediction of interactomes for experimental validation.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241304666"},"PeriodicalIF":2.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812150","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":"Comprehensive Analysis of the Influence of Technical and Biological Variations on De Novo Assembly of RNA-Seq Datasets.","authors":"Gonzalez Sergio Alberto, Rivarola Maximo, Ribone Andres, Lew Sergio, Paniego Norma","doi":"10.1177/11779322241274957","DOIUrl":"10.1177/11779322241274957","url":null,"abstract":"<p><p>De novo assembly of transcriptomes from species without reference genome remains a common problem in functional genomics. While methods and algorithms for transcriptome assembly are continually being developed and published, the quality of de novo assemblies using short reads depends on the complexity of the transcriptome and is limited by several types of errors. One problem to overcome is the research gap regarding the best method to use in each study to obtain high-quality de novo assembly. Currently, there are no established protocols for solving the assembly problem considering the transcriptome complexity. In addition, the accuracy of quality metrics used to evaluate assemblies remains unclear. In this study, we investigate and discuss how different variables accounting for the complexity of RNA-Seq data influence assembly results independently of the software used. For this purpose, we simulated transcriptomic short-read sequence datasets from high-quality full-length predicted transcript models with varying degrees of complexity. Subsequently, we conducted de novo assemblies using different assembly programs, and compared and classified the results using both reference-dependent and independent metrics. These metrics were assessed both individually and combined through multivariate analysis. The degree of alternative splicing and the fragment size of the paired-end reads were identified as the variables with the greatest influence on the assembly results. Moreover, read length and fragment size had different influences on the reconstruction of longer and shorter transcripts. These results underscore the importance of understanding the composition of the transcriptome under study, and making experimental design decisions related to the need to work with reads and fragments of different sizes. In addition, the choice of assembly software will positively impact the final assembly outcome. This selection will affect the completeness of represented genes and assembled isoforms, as well as contribute to error reduction.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241274957"},"PeriodicalIF":2.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799395","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":"Exploring LDLR-APOB Interactions in Familial Hypercholesterolemia in the Vietnamese Population: A Protein-Protein Docking Approach.","authors":"Ngoc-Thanh Kim, Doan-Loi Do, Mai-Ngoc Thi Nguyen, Hong-An Le, Thanh-Tung Le, Thanh-Huong Truong","doi":"10.1177/11779322241301267","DOIUrl":"https://doi.org/10.1177/11779322241301267","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular diseases (CVDs) are closely linked to factors such as familial hypercholesterolemia (FH), often caused by mutations in low-density lipoprotein receptor (<i>LDLR</i>) and apolipoprotein B (<i>APOB</i>). Through a comprehensive bioinformatic analysis, we identified novel <i>LDLR</i> and <i>APOB</i> mutations and their cardiovascular disease (CVD) implications, focusing on unique variants in the Vietnamese population. We used homology modeling to predict protein structures; in addition, through protein-protein molecular docking, we assessed how these mutations affect binding affinities. We identified 10 novel binding residues exclusive to the wild-type and precursor LDLR isoforms, including ASP-47, GLY-48, and GLU-51. Analyses of 154 complexes revealed 5 isoforms with low binding affinities and notable hydrogen-bonding interactions-APOB (Arg3527Trp)-LDLR (Cys318Arg), APOB (His3583Leu)-LDLR (Cys104Tyr), APOB wild-LDLR (Glu228Lys), APOB (Phe2469Cys)-LDLR (Glu288Lys), and APOB wild-LDLR (Ser130Ter). These results suggest strong and potentially detrimental interactions among these proteins. Furthermore, they highlight the molecular mechanisms underlying CVD development, reveal potential therapeutic targets, enhance our understanding of genetic variations, and could guide FH research.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241301267"},"PeriodicalIF":2.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765957","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":"Mechanistic Insights of hsa-mir-301a Regulation by Tobacco Smoke in Lung Squamous Cell Carcinoma: Evidence From Bioinformatics Analysis.","authors":"Vladimir O Pustylnyak, Alina M Perevalova, Lyudmila F Gulyaeva","doi":"10.1177/11779322241302168","DOIUrl":"https://doi.org/10.1177/11779322241302168","url":null,"abstract":"<p><p>MicroRNAs play a significant role in the development of cancers, including lung cancer. A recent study revealed that smoking, a key risk factor for lung cancer, increased the levels of hsa-mir-301a in the tumor tissues of patients with lung squamous cell carcinoma (LUSC). The aim of the current study is to investigate the mechanism by which tobacco smoke increases hsa-mir-301a levels in LUSC tumor tissues using bioinformatics analysis. Bioinformatics tools and online databases, including The Cancer Genome Atlas (TCGA), LinkedOmics, and Encyclopedia of RNA Interactomes (ENCORI), were applied in this study. Our results showed a correlation between the upregulation of hsa-mir-301a in LUSC tissues and smoking exposure. However, no correlation was discovered between patients' smoking status and the expression level of the hsa-mir-301a host gene, <i>SKA2</i>, prompting us to investigate possible changes in microRNA processing under tobacco smoke exposure. In silico results using online platforms suggest that post-transcriptional processes, which involve the RNA-binding proteins DGCR8 and FUS, contribute to the elevation of mature hsa-mir-301a levels in smoking patients with LUSC. Our findings suggest that RNA-binding proteins play a key role in controlling the processing of hsa-mir-301a, indicating a complex regulation of hsa-mir-301a in the LUSC tissues of smokers.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241302168"},"PeriodicalIF":2.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765960","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":"System Genetics Analysis Reveals Sex Differences in Human Aortic Smooth Muscle Gene Expression.","authors":"Sarah L Meng, Rita Anane-Wae, Ernest Diez Benavente, Redouane Aherrahrou","doi":"10.1177/11779322241298592","DOIUrl":"https://doi.org/10.1177/11779322241298592","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery disease (CAD) is one of the leading causes of death worldwide. The buildup of atherosclerotic plaque, including lipids and cellular waste, characterizes this disease. Smooth muscle cells (SMCs) can migrate and proliferate to form a fibrous cap that stabilizes the atherosclerotic plaque in response to plaque buildup. However, in some severe cases, the fibrous cap is unable to prevent plaque rupture, which can lead to a thrombotic event causing a stroke or myocardial infarction. Studies have been conducted to identify genes associated with this disease. However, the influence of sex on CAD risk is poorly understood due to the complexity of the disease and the lack of women in clinical studies.</p><p><strong>Methods: </strong>This study is investigated with a unique collection of human aortic smooth muscle cells (huASMCs) derived from 118 male and 33 female individuals who either underwent a heart transplant or were victims of motor vehicle accidents. In this investigation, we explore differentially expressed genes between males and females related to atherosclerosis using a unique RNAseq dataset of human aortic SMCs.</p><p><strong>Results: </strong>Our study identified 8 genes (<i>CHST1, DKK2, DLL4, EIF1AXP1, GALNT13, NOTCH4, SELL, SPARCL1</i>) that exhibit sex-biased effects in SMCs. Of these, 6 genes were found in the Athero-Express dataset and 5 of them were associated with atherosclerosis-relevant phenotypes. We discovered a novel NOTCH4/DLL4 pathway that plays a role in the differential expression of these genes between males and females. This pathway is linked to coronary artery physiology and may play a role in the pathophysiology of coronary artery disease that differs between the sexes.</p><p><strong>Conclusions: </strong>Overall, this investigation shows that differentially expressed genes between males and females in human aortic SMCs exist.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241298592"},"PeriodicalIF":2.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765961","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":"Regulatory Element Analysis and Comparative Genomics Study of Heavy Metal-Resistant Genes in the Complete Genome <i>of Cupriavidus gilardii</i> CR3.","authors":"Duguma Dibbisa, Tadesse Daba, Seid Mohammed","doi":"10.1177/11779322241299905","DOIUrl":"10.1177/11779322241299905","url":null,"abstract":"<p><p>Environmental pollution has become a worldwide concern that requires rigorous efforts from all sectors of society to monitor, control, and remediate it. In environmental pollution control, <i>Cupriavidus gilardii</i> CR3 has become a model organism to study resistance to heavy metals as a means of bacterial bioremediation. This research aimed to single out regulatory element analysis and conduct a comparative genome study of the heavy metal resistance genes in the complete genome of <i>C gilardii</i> CR3 using bioinformatics and omics tools. Comparative genome analysis, promoter prediction, common motif identification, transcriptional start site identification, gene annotation, and transcription factor identification search are the major steps to understanding gene expression and regulation. MEME Suit, TOMTOM, Prokka, Rapid Annotation utilizing Subsystem Technology (RAST), Orthologous Average Nucleotide Identity Software Tool (OAT), and EziBio databases or programs were the major tools used in this study. Fourteen transcriptional factors were identified and predicted from the most credible and lowest candidate motifs with an e-value of 3.0e-009, which was statistically the utmost remarkable candidate motif. A detailed evaluation was further performed, and 14 transcriptional factors were identified as in activation, repression, and dual functions. The data revealed that most transcriptional factors identified were used for activation rather than repression. The <i>C gilardii</i> CR3 genome contains many genes responsible for resisting heavy metals such as mercury, cadmium, zinc, copper, and arsenate. As a result, regulatory elements will lay a solid basis for understanding genes responsible for heavy metal bioremediation. It was concluded that further studies with wet lab support could be conducted for confirmation. Moreover, other advanced bioinformatics and omics technologies are needed to strengthen the results.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241299905"},"PeriodicalIF":2.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715205","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":"Haplotypic Distribution of SARS-CoV-2 Variants in Cases of Intradomiciliary Infection in the State of Rondônia, Western Amazon.","authors":"Karolaine Santos Teixeira, Márlon Grégori Flores Custódio, Gabriella Sgorlon, Tárcio Peixoto Roca, Jackson Alves da Silva Queiroz, Ana Maisa Passos-Silva, Jessiane Ribeiro, Deusilene Vieira","doi":"10.1177/11779322241266354","DOIUrl":"10.1177/11779322241266354","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high transmissibility profile which favors the accumulation of mutations along its genome, providing the emergence of new variants. In this context, haplotype studies have allowed mapping specific regions and combining approaches and tracking phylogenetic changes. During the COVID-19 pandemic, it was notorious that home environments favored the circulation of SARS-CoV-2, in this study we evaluated 1,407 individuals positive for SARS-CoV-2, in which we located 53 families in the period from June 2021 to February 2023. The epidemiological data were collected in E-SUS notifica and SIVEP-gripe. Then, the genetic material was extracted using the commercial kit and the viral load was evaluated and the viral genomes were sequenced using the Illumina MiSeq methodology. In addition, the circulation of 3 variants and their respective subvariants was detected. The delta variant represented the highest number of cases with 45%, the Omicron variant 43% and the lowest number with 11% of cases the Gamma variants. There were cases of families infected by different subvariants, thus showing different sources of infection. The haplotype network showed a distribution divided into 6 large clusters that were established according to the genetic characteristics observed by the algorithm and 224 Parsimony informative sites were found. In addition, 92% of subjects were symptomatic and 8% asymptomatic. The secondary attack rate of this study was 8.32%. Therefore, we can infer that the home environment favors the spread of SARS-CoV-2, so it is of paramount importance to carry out genomic surveillance in specific groups such as intradomiciliary ones.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241266354"},"PeriodicalIF":2.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685917","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":"The TWW Growth Model and Its Application in the Analysis of Quantitative Polymerase Chain Reaction.","authors":"M Tabatabai, D Wilus, K P Singh, T L Wallace","doi":"10.1177/11779322241290126","DOIUrl":"10.1177/11779322241290126","url":null,"abstract":"<p><p>It is necessary to accurately capture the growth trajectory of fluorescence where the best fit, precision, and relative efficiency are essential. Having this in mind, a new family of growth functions called TWW (Tabatabai, Wilus, Wallace) was introduced. This model is capable of accurately analyzing quantitative polymerase chain reaction (qPCR). This new family provides a reproducible quantitation of gene copies and is less labor-intensive than current quantitative methods. A new cycle threshold based on TWW that does not need the assumption of equal reaction efficiency was introduced. The performance of TWW was compared with 3 classical models (Gompertz, logistic, and Richard) using qPCR data. TWW models the relationship between the cycle number and fluorescence intensity, outperforming some state-of-the-art models in performance measures. The 3-parameter TWW model had the best model fit in 68.57% of all cases, followed by the Richard model (28.57%) and the logistic (2.86%). Gompertz had the worst fit in 88.57% of all cases. It had the best precision in 85.71% of all cases followed by Richard (14.29%). For all cases, Gompertz had the worst precision. TWW had the best relative efficiency in 54.29% of all cases, while the logistic model was best in 17.14% of all cases. Richard and Gompertz tied for the best relative efficiency in 14.29% of all cases. The results indicate that TWW is a good competitor when considering model fit, precision, and efficiency. The 3-parameter TWW model has fewer parameters when compared to the Richard model in analyzing qPCR data, which makes it less challenging to reach convergence.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241290126"},"PeriodicalIF":2.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680788","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":"Unlocking Benzosampangine's Potential: A Computational Approach to Investigating, Its Role as a PD-L1 Inhibitor in Tumor Immune Evasion via Molecular Docking, Dynamic Simulation, and ADMET Profiling.","authors":"Abderrahim Ait Ouchaoui, Salah Eddine El Hadad, Marouane Aherkou, Elkamili Fadoua, Mkamel Mouad, Youssef Ramli, Anass Kettani, Ilhame Bourais","doi":"10.1177/11779322241298591","DOIUrl":"10.1177/11779322241298591","url":null,"abstract":"<p><p>The interaction between programmed cell death protein 1 (PD-1) and its ligand PD-L1 plays a crucial role in tumor immune evasion, presenting a critical target for cancer immunotherapy. Despite being effective, current monoclonal antibodies present some drawbacks such as high costs, toxicity, and resistance development. Therefore, the development of small-molecule inhibitors is necessary, especially those derived from natural sources. In this study, benzosampangine is predicted as a promising PD-L1 inhibitor, with potential applications in cancer immunotherapy. Utilizing the high-resolution crystal structure of human PD-L1 (PDB ID: 5O45), we screened 511 natural compounds, identifying benzosampangine as a top candidate with exceptional inhibitory properties. Molecular docking predicted that benzosampangine exhibits a strong binding affinity for PD-L1 (-9.4 kcal/mol) compared with established controls such as CA-170 (-6.5 kcal/mol), BMS-202 (-8.6 kcal/mol), and pyrvinium (-8.9 kcal/mol). The compound's predicted binding efficacy is highlighted by robust interactions with key amino acids (ILE54, TYR56, GLN66, MET115, ILE116, SER117, ALA121, ASP122) within the active site, notably forming 3 Pi-sulfur interactions with MET115-an interaction absents in control inhibitors. In addition, ADMET profiling suggests that over the control molecules, benzosampangine has several key advantages, including favorable solubility, permeability, metabolic stability, and low toxicity, while adhering to Lipinski's rule of five. Molecular dynamic simulations predict the stability of the benzosampangine-PD-L1 complex, reinforcing its potential to sustain inhibition of the PD-1/PD-L1 pathway. MMGBSA analysis calculated a binding free energy (ΔGbind) of -39.39 kcal/mol for the benzosampangine-PD-L1 complex, with significant contributions from Coulombic, lipophilic, and Van der Waals interactions, validating the predicted docking results. This study investigates in silico benzosampangine, predicting its better molecular interactions and pharmacokinetic profile compared with several already known PD-L1 inhibitors.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241298591"},"PeriodicalIF":2.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675160","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":"Drug Repositioning for Scorpion Envenomation Treatment Through Dual Inhibition of Chlorotoxin and Leiurotoxin.","authors":"Gaouzi Zainab, Abbou Hanane, Zegrari Razana, Eljaoudi Rachid, Diawara Idrissa, Hakmi Mohammed, Mkamel Mouad","doi":"10.1177/11779322241294130","DOIUrl":"https://doi.org/10.1177/11779322241294130","url":null,"abstract":"<p><p>Scorpion envenomation, a grave public health concern, is primarily driven by the potent neurotoxins chlorotoxin and leiurotoxin present in Leiurus species venom. Developing effective treatments is crucial to mitigate its impact. Utilizing a drug-repositioning bioinformatics-based approach, potential inhibitors of these neurotoxins were identified from Food and Drug Administration (FDA)-approved drugs. Through virtual screening and subsequent molecular dynamics simulations, their ability to stabilize the peptides over time was evaluated. Among the compounds scrutinized, bolazine emerged as a promising candidate, demonstrating significant affinity for both neurotoxins, indicating potential dual inhibitory activity. Molecular dynamics simulations further corroborated the enhanced stability of bolazine complexes compared to neurotoxins alone. These findings suggest the feasibility of repurposing existing drugs to develop new therapeutic strategies to treat scorpion envenomation. Such interventions hold promise in alleviating the severe health repercussions of scorpion stings and meeting the urgent demand for effective remedies in affected communities.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241294130"},"PeriodicalIF":2.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614604","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}