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Multi-epitope-based vaccine models prioritization against Astrovirus MLB1 using immunoinformatics and reverse vaccinology approaches 利用免疫信息学和反向疫苗学方法确定星状病毒MLB1多表位疫苗模型的优先级
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-12-16 DOI: 10.1016/j.jgeb.2024.100451
Awais Ali , Syed Luqman Ali , Abdulaziz Alamri , Elham Mohammed Khatrawi , Aliya Baiduissenova , Fatima Suleimenova , Vipin Kumar Mishra , Asifullah Khan , Marat Dusmagambetov , Gulsum Askarova
{"title":"Multi-epitope-based vaccine models prioritization against Astrovirus MLB1 using immunoinformatics and reverse vaccinology approaches","authors":"Awais Ali ,&nbsp;Syed Luqman Ali ,&nbsp;Abdulaziz Alamri ,&nbsp;Elham Mohammed Khatrawi ,&nbsp;Aliya Baiduissenova ,&nbsp;Fatima Suleimenova ,&nbsp;Vipin Kumar Mishra ,&nbsp;Asifullah Khan ,&nbsp;Marat Dusmagambetov ,&nbsp;Gulsum Askarova","doi":"10.1016/j.jgeb.2024.100451","DOIUrl":"10.1016/j.jgeb.2024.100451","url":null,"abstract":"<div><div>Astrovirus MLB1 (HAstV-MLB1) is non-enveloped RNA virus that cause acute gastroenteritis infection. Despite research progress about infection and pathogenesis of HAstV-MLB1, Currently, no vaccine has been developed to effectively combat this pathogen. The current study is based on immunoinformatics and reverse vaccinology approaches to design next-generation, multi-epitope-based vaccine models against HAstV-MLB1. Genome-wide whole proteome data of HAstV-MLB1 strain was retrieved, and a series of analyses were conducted to explore effective B and T-cell epitopes that hold significant antigenic nature with no toxicity and allergenicity. A set of vaccine constructs were designed by different combination of lead B and T-cell epitopes with diverse linkers and adjuvants sequences. The model vaccine structures were analyzed via rigorous criteria of physiochemical properties, antigenicity, and molecular docking with HLA and TLR4 immune receptors to ensure their efficacy and safety. Based on the lowest binding energy of −82.48 kcal/mol against the HLA receptor, the MLB1-C2 vaccine model with β-definsin adjuvant was prioritized for molecular dynamic and immune simulations analyses to assess its stability and immunogenic potential. These analyses revealed that the MLB1-C2 construct has feasible molecular stability and potential to boost strong immune responses in the host cell. Besides, the model was predicted to be non-toxic, non-allergenic, and antigenic, ensuring broad population coverage and capable to elicit a robust immune response. The <em>in-silico</em> cloning analysis highlighted a possible gene expression potential of the MLB1-C2 construct in <em>E.coli</em> commercial recombinant vector molecule. The findings of the current study provide an essential template for the development of a advanced next-generation effective vaccine against HAstV-MLB1.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100451"},"PeriodicalIF":3.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128890","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}
引用次数: 0
A convenient viral transduction based method for advanced multi-engineering of primary human (CAR) T-cells 一种便捷的基于病毒转导的原代人(CAR) t细胞高级多工程方法
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-12-01 DOI: 10.1016/j.jgeb.2024.100446
Jort J van der Schans, Afroditi Katsarou, George Kladis, Citlali Bar, Max Medina Ramirez, Maria Themeli, Tuna Mutis
{"title":"A convenient viral transduction based method for advanced multi-engineering of primary human (CAR) T-cells","authors":"Jort J van der Schans,&nbsp;Afroditi Katsarou,&nbsp;George Kladis,&nbsp;Citlali Bar,&nbsp;Max Medina Ramirez,&nbsp;Maria Themeli,&nbsp;Tuna Mutis","doi":"10.1016/j.jgeb.2024.100446","DOIUrl":"10.1016/j.jgeb.2024.100446","url":null,"abstract":"<div><div>The past decades have illustrated the power of T-cell engineering in the development of new and successful cell therapies, such as chimeric antigen receptor (CAR) T-cells. Despite clinical success in hematological malignancies, it also becomes increasingly clear that additional T-cell engineering will be required to improve efficacy and safety and expand the application to solid tumors. Engineering is most often achieved by viral delivery of transgenes, however, viral vector capacity limitations make efficient and reproducible generation of multi transgene expressing T-cell therapeutics technically challenging. We here describe a convenient and efficient method for the delivery of up to three γ-retroviral CAR vectors in T-cells. We achieved this using virus vector mixtures that are simultaneously produced at high titers by double- or triple- transduced stable virus producer cells. We show that this method is superior in overall efficiency and reproducibility to conventional double or triple CAR transductions, in which separate viral batches are used. Due to its robustness, this method can facilitate the research and the development for advanced T-cell engineering towards more effective and safe therapies.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100446"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744358","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}
引用次数: 0
Identification and characterization of Capsicum mutants using, biochemical, physiological, and single sequence repeat (SSR) markers 利用生化、生理和单序列重复(SSR)标记对辣椒突变体进行鉴定和鉴定。
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-12-01 DOI: 10.1016/j.jgeb.2024.100447
Nazarul Hasan , Sana Choudhary , Neha Naaz , Nidhi Sharma , Shahabab Ahmad Farooqui , Megha Budakoti , Dinesh Chandra Joshi
{"title":"Identification and characterization of Capsicum mutants using, biochemical, physiological, and single sequence repeat (SSR) markers","authors":"Nazarul Hasan ,&nbsp;Sana Choudhary ,&nbsp;Neha Naaz ,&nbsp;Nidhi Sharma ,&nbsp;Shahabab Ahmad Farooqui ,&nbsp;Megha Budakoti ,&nbsp;Dinesh Chandra Joshi","doi":"10.1016/j.jgeb.2024.100447","DOIUrl":"10.1016/j.jgeb.2024.100447","url":null,"abstract":"<div><div>Identification and characterization of crop mutants through molecular marker analysis are imperious to develop desirable traits in mutation breeding programs. In the present study, macromolecular variations with altered morphological, quantitative, and biochemical traits were generated through chemically induced mutagenesis via alkylating agents and heavy metals. Statistical analysis based on quantitative traits indicating enhanced mean value in mutant lines selected from the M<sub>4</sub> generation as compared to previous generations. Identification and characterization of morphology in selected mutant lines are based on altered phenotypes (e.g. tall and dwarf mutant with high yield, fruits with thick texture and bold seeds, etc.) in comparison to control populations. The useful mutations were recorded in phytochemicals (e.g. capsaicin and dihydrocapsaicin) and macro and micro nutrients profile (e.g. protein, iron, copper, cadmium and zinc) in selected mutant lines of <em>Capsicum annuum</em> L. Single Sequence Repeats (SSRs) markers analysis in selected mutant lines revealed genetic diversity in <em>Capsicum. annuum</em> L. The total of 44 alleles were observed with average number of allele 4.00. The Unweighted Pair Group Arithmetic Mean Method (UPGMA) showed maximum dissimilarity was recorded between mutant A-III and F-III followed by mutant G-III and C-III, while mutant B-III and G-III showed the lowest dissimilarity to each other followed by mutant L-III and mutant J-III. Correlation and Principal Component Analysis (PCA) revealed genetic diversity among mutant lines indicating their prioritization over other traits in indirect selection and also revealed that mutants treated with lower and medium concentrations were divergent. These mutant lines could be suitable in crop improvement programs for the broadening the genetic base of <em>C. annuum</em> L. Hierarchical Cluster Analysis (HCA) grouped the mutants into two clusters with variable euclidean distance indicated heterogeneous mutant lines developed from induced mutagenic treatments. Thus beneficial mutations could be induced in chilli genotypes via mutation breeding to enhance genetic variability in limited resources, period, and efforts.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100447"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824971","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}
引用次数: 0
The current status of genetic biofortification in alleviating malnutrition in Africa 基因生物强化在减轻非洲营养不良方面的现状
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-11-27 DOI: 10.1016/j.jgeb.2024.100445
Gideon Sadikiel Mmbando, Julius Missanga
{"title":"The current status of genetic biofortification in alleviating malnutrition in Africa","authors":"Gideon Sadikiel Mmbando,&nbsp;Julius Missanga","doi":"10.1016/j.jgeb.2024.100445","DOIUrl":"10.1016/j.jgeb.2024.100445","url":null,"abstract":"<div><div>Africa is a continent where undernutrition and micronutrient deficiencies are common and malnutrition is a major problem. Genetic biofortification (GB) offers a promising way to combat malnutrition. But little is still known about how widely used GB is in Africa today. This review explores the status, achievements, and challenges of GB on the continent today. It draws attention to the potential for enhanced nutritional results from biofortified crops that are enhanced with vital elements like zinc, iron, and vitamin A. Biofortification has a demonstrable positive effect on health and wellness, as evidenced by success stories from several African nations. However, obstacles like a lack of farmer awareness, difficulty obtaining biofortified seeds, and complicated regulations make adoption difficult. Research and collaboration advances hold the potential for increasing GB’s effectiveness. This study offers guidance for the future and calls for coordinated efforts to implement GB programs to achieve a well-nourished Africa.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100445"},"PeriodicalIF":3.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721550","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}
引用次数: 0
Comprehensive virome profiling of sugarcane and simplified duplex OneStep RT-PCR assay reveals the prevalence of sugarcane streak mosaic virus along with sugarcane yellow leaf virus in India 甘蔗病毒组综合分析和简化的双联 OneStep RT-PCR 检测揭示了甘蔗条纹花叶病毒和甘蔗黄叶病毒在印度的流行情况
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-11-26 DOI: 10.1016/j.jgeb.2024.100442
Nishant Srivastava , Malyaj R. Prajapati , Rakesh Kumar , Pooja Bhardwaj , Nitika Gupta , Vanita Chandel , Susheel K. Sharma , Virendra K. Baranwal
{"title":"Comprehensive virome profiling of sugarcane and simplified duplex OneStep RT-PCR assay reveals the prevalence of sugarcane streak mosaic virus along with sugarcane yellow leaf virus in India","authors":"Nishant Srivastava ,&nbsp;Malyaj R. Prajapati ,&nbsp;Rakesh Kumar ,&nbsp;Pooja Bhardwaj ,&nbsp;Nitika Gupta ,&nbsp;Vanita Chandel ,&nbsp;Susheel K. Sharma ,&nbsp;Virendra K. Baranwal","doi":"10.1016/j.jgeb.2024.100442","DOIUrl":"10.1016/j.jgeb.2024.100442","url":null,"abstract":"<div><h3>Background</h3><div>Sugarcane is host of many viral pathogens that affects its growth and productivity<strong>.</strong> High-throughput sequencing (HTS) is comprehensive diagnostic platform that permit the precise detection of viral pathogens to resolve the disease epidemiology of the crop, thus providing the phytosanitary status of plants. The current work was designed to comprehend the virome profiling of sugarcane belonging to five varieties collected from the major crop producing states in India. Additionally, a duplex OneStep RT-PCR assay was optimized for simplified detection of prevalent viruses in single reaction run along with validation and confirmation of HTS results.</div></div><div><h3>Results</h3><div>The complete genome sequences of sugarcane streak mosaic virus (SCSMV), sugarcane yellow leaf virus (SCYLV) and sugarcane mosaic virus (SCMV) consisted of 9790, 5849 and 9600 nucleotides (nt) respectively were obtained excluding 5′ UTR and 3′ poly (A) tail from sugarcane samples belonging to different varieties. SCSMV and SCMV had single ORF encoding 3130 and 3063 amino acids (aa) respectively, whereas SCYLV genome comprised of six ORFs. The proteolytic cleavage sites in polyprotein region of SCSMV and SCMV revealed the unique amino acid motifs. SCSMV generated the highest number of single nucleotide variants (SNVs) 876 suggesting that it is more susceptible to mutations than other elucidated viruses in HTS. Recombination events revealed the origin of SCSMV_UP isolate from Indian and Iranian isolates as major and minor parents respectively. Further, validation assay by simplified duplex OneStep RT-PCR revealed the prevalence of SCSMV and SCYLV as mixed infection in sugarcane samples with 28 % incidence. The assay could detect the viruses up to 100 pg/µL of RNA concentration.</div></div><div><h3>Conclusion</h3><div>The first comprehensive report of sugarcane virome and use of an optimized duplex OneStep RT-PCR assay revealed the prevalence of SCSMV and SCYLV in sugarcane from India. The study also provides an insight into genetic variations in the coding region of SCSMV and SCMV and emergence of diverse variants present in a viral population. A simplified duplex OneStep RT-PCR assay for simultaneous and expeditious detection of prevalent viruses in sugarcane would be useful in certification programme for production of virus-free planting materials.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100442"},"PeriodicalIF":3.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700508","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}
引用次数: 0
Genome-wide identification and expression analysis of the MORF gene family in celery reveals their potential role in chloroplast development 芹菜中 MORF 基因家族的全基因组鉴定和表达分析揭示了它们在叶绿体发育中的潜在作用
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-11-22 DOI: 10.1016/j.jgeb.2024.100443
Pei-Zhuo Liu , Ya-Hui Wang , Yue-Hua Sun , Yong-Ju Wei , Xu Sun , Meng-Yao Li , Guo-Fei Tan , Ai-Sheng Xiong
{"title":"Genome-wide identification and expression analysis of the MORF gene family in celery reveals their potential role in chloroplast development","authors":"Pei-Zhuo Liu ,&nbsp;Ya-Hui Wang ,&nbsp;Yue-Hua Sun ,&nbsp;Yong-Ju Wei ,&nbsp;Xu Sun ,&nbsp;Meng-Yao Li ,&nbsp;Guo-Fei Tan ,&nbsp;Ai-Sheng Xiong","doi":"10.1016/j.jgeb.2024.100443","DOIUrl":"10.1016/j.jgeb.2024.100443","url":null,"abstract":"<div><div>Chlorophyll is an important nutrient in celery and one of the main indexes of quality evaluation. RNA editing in chloroplasts is an important factor affecting chloroplast development and chlorophyll biosynthesis. Multisite organelle RNA editing factor (MORF) protein is a necessary regulator of chloroplast RNA editing. In this study, a total of 8 <em>MORF</em> genes in celery were identified, which were named <em>AgMORF1a</em>, <em>AgMORF1b</em>, <em>AgMORF2a</em>, <em>AgMORF2b</em>, <em>AgMORF3</em>, <em>AgMORF7</em>, <em>AgMORF8</em> and <em>AgMORF9</em> according to their subfamily classification. The physicochemical property, conserved motifs, <em>cis</em>-acting elements and protein interaction were predicted according to the sequences. The phylogenetic relationships and evolutionary selective pressure between <em>MORF</em> genes in celery and other Apiaceae plants were further analyzed. The results showed that <em>AgMORF1b</em>, <em>AgMORF2a</em>, <em>AgMORF2b</em> and <em>AgMORF9</em> were predicted to be localized in chloroplasts. The evolution of <em>MORF</em> genes in 4 Apiaceae plants including celery, carrot, coriander and water dropwort was influenced by purify selection. Transcriptome data showed that the transcriptional levels of <em>AgMORF2a</em>, <em>AgMORF2b</em>, <em>AgMORF8</em> and <em>AgMORF9</em> were relatively higher among all <em>MORF</em> genes in petioles of celery, indicating their major role. RT-qPCR data showed that the expression levels of the above 4 genes were significantly higher in petioles of green celery than those of white celery. This study provided a basis for analyzing the effects of MORF proteins on chloroplast development of celery with different chlorophyll accumulation.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100443"},"PeriodicalIF":3.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700595","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}
引用次数: 0
Adropin a candidate diagnostic biomarker for cardiovascular disease in patients with chronic kidney disease 慢性肾病患者心血管疾病的候选诊断生物标志物--阿托品
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-11-20 DOI: 10.1016/j.jgeb.2024.100438
Maha Abd El Moneem Elfedawy , Samia Abd El Sadek Elsebai , Hend Mohamed Tawfik , Eman Refaat Youness , Moushira Zaki
{"title":"Adropin a candidate diagnostic biomarker for cardiovascular disease in patients with chronic kidney disease","authors":"Maha Abd El Moneem Elfedawy ,&nbsp;Samia Abd El Sadek Elsebai ,&nbsp;Hend Mohamed Tawfik ,&nbsp;Eman Refaat Youness ,&nbsp;Moushira Zaki","doi":"10.1016/j.jgeb.2024.100438","DOIUrl":"10.1016/j.jgeb.2024.100438","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) is a chief worldwide health concern that has a substantial financial impact on health systems, high rates of mortality and morbidity as well as cardiovascular disease (CVD) is a major cause of mortality in this population. Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene.</div></div><div><h3>Aim of the work</h3><div>We aimed to explore the efficacy of adropin as a diagnostic candidate biomarker for CVD in patients with CKD.</div></div><div><h3>Methods</h3><div>This is prospective study was carried out on 60 patients (Pt) with CKD and 30 age and sex matched healthy control subjects. CKD Pt were classified according to the history of CVD into two groups: Group A, Pt without history (n = 32) and Group B, Pt with history (n = 28). Serum adropin, lipids and Hs-CRP were measured by ELISA kit. Echocardiography was also investigated. Receiver operator characteristic curve (ROC) was used to determine cut-off points of adropin. Negative predict value (NPV), negative predict value (NPV) and area under curve were detected.</div></div><div><h3>Results</h3><div>There were abnormal ECGs in 78.6 % of CKD patients. Adropin was significantly decreased in Group B than Group A and control group. On the other hand, serum lipids and Hs-CRP were significantly increased in Group B than Group A and control group. ROC analysis revealed that serum adropin could be used to discriminate between patients with and without CVD history at a cutoff level of &gt; 304 with 46.4 % sensitivity and 84.4 % specificity, 74.8 % PPV, 61.2 % NPV and AUC = 0.57. Moreover, between Group A and control at a cutoff level of &lt; 410, with 93.8 % sensitivity, 86.7 % specificity, 87.6 % PPV and 93.3 % NPV and AUC = 0.97 as well as between Group B and control group at a cutoff level of &lt; 416, with 57.1 % sensitivity, 83.3 % specificity, 77.4 % PPV and 66 % NPV and AUC = 0.65.</div></div><div><h3>Conclusion</h3><div>Particularly in CKD patients, adropin may be a useful biomarker for predicting the onset of CVD. Adropin may represent a novel and useful blood marker for assessing systolic function and Spontaneous coronary artery dissection (SCAD).</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100438"},"PeriodicalIF":3.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700507","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}
引用次数: 0
Fungal secondary metabolites as a potential inhibitor of T315I- BCR::ABL1 mutant in chronic myeloid leukemia by molecular docking, molecular dynamics simulation and binding free energy exploration approaches 通过分子对接、分子动力学模拟和结合自由能探索方法,将真菌次生代谢物作为慢性髓性白血病 T315I- BCR::ABL1 突变体的潜在抑制剂
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-11-20 DOI: 10.1016/j.jgeb.2024.100444
Dilinazi Abulaiti, Niluopaer Tuerxun, Huan Wang, Lina Ma, Fang Zhao, Yang Liu, Jianping Hao
{"title":"Fungal secondary metabolites as a potential inhibitor of T315I- BCR::ABL1 mutant in chronic myeloid leukemia by molecular docking, molecular dynamics simulation and binding free energy exploration approaches","authors":"Dilinazi Abulaiti,&nbsp;Niluopaer Tuerxun,&nbsp;Huan Wang,&nbsp;Lina Ma,&nbsp;Fang Zhao,&nbsp;Yang Liu,&nbsp;Jianping Hao","doi":"10.1016/j.jgeb.2024.100444","DOIUrl":"10.1016/j.jgeb.2024.100444","url":null,"abstract":"<div><h3>Background</h3><div>Chronic Myeloid Leukemia (CML) is particularly challenging to treat due to the T315I BCR::ABL1 mutation. Although fungal metabolites are known for their pharmaceutical potential, none are approved for CML. Our study screened approximately 2000 fungal secondary metabolites to discover inhibitors targeting the T315I- BCR::ABL1 mutant protein.</div></div><div><h3>Methods</h3><div>We conducted comprehensive analyses to elucidate the interactions between the T315I-BCR::ABL1 mutant protein and selected fungal metabolites. These analyses included molecular docking, ADMET assessment, molecular dynamics simulations, principal components analysis, exploration of free energy landscapes, and per-residue decomposition.</div></div><div><h3>Results</h3><div>We identified a range of binding affinities for fungal secondary metabolites, from −11.2 kcal/mol to −2.90 kcal/mol, with the co-crystal ponatinib showing a binding affinity of −9.9 kcal/mol. Notably, twenty seven fungal metabolites had affinities ≤ -10.0 kcal/mol, surpassing ponatinib. Eight compounds, including Phellifuropyranone A and Meshimakobnol B, showed favorable drug-likeness. Molecular dynamics parameters, including RMSD, RMSF, Rg, and SASA, confirmed that Phellifuropyranone A and Meshimakobnol B bind stably to the T315I-BCR::ABL1 mutant protein. Additionally, PCA, DCCM, and free energy landscapes analyses validated the consistency of the molecular dynamics parameters. MM/PBSA analysis indicated that Phellifuropyranone A (–22.88 ± 4.28 kcal/mol) and Meshimakobnol B (−25.86 ± 3.51 kcal/mol) bind similarly to ponatinib (−25.54 ± 6.31 kcal/mol). Per-residue decomposition explored residues MET290, VAL299, ILE315, and PHE359 as crucial for binding to the T315I-BCR::ABL1 mutant protein.</div></div><div><h3>Conclusions</h3><div>Phellifuropyranone A and Meshimakobnol B show significant potency as inhibitors of the T315I-BCR::ABL1 mutant protein, comparable to ponatinib. These compounds may serve as effective alternatives or synergistic agents with ponatinib, potentially overcoming drug resistance and improving treatment outcomes in Chronic Myeloid Leukemia.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100444"},"PeriodicalIF":3.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700594","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}
引用次数: 0
Exploring advanced genomic and immunoinformatics techniques for identifying drug and vaccine targets against SARS-CoV-2 探索先进的基因组学和免疫信息学技术,以确定抗击 SARS-CoV-2 的药物和疫苗靶点
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-11-16 DOI: 10.1016/j.jgeb.2024.100439
Syed Luqman Ali , Awais Ali , Waseef Ullah , Abdulaziz Alamri , Elham Mohammed Khatrawi , Gulzira Sagimova , Aigul Almabayeva , Farida Rakhimzhanova , Gulsum Askarova , Fatima Suleimenova , Nabras Al-Mahrami , Prasanta Kumar Parida
{"title":"Exploring advanced genomic and immunoinformatics techniques for identifying drug and vaccine targets against SARS-CoV-2","authors":"Syed Luqman Ali ,&nbsp;Awais Ali ,&nbsp;Waseef Ullah ,&nbsp;Abdulaziz Alamri ,&nbsp;Elham Mohammed Khatrawi ,&nbsp;Gulzira Sagimova ,&nbsp;Aigul Almabayeva ,&nbsp;Farida Rakhimzhanova ,&nbsp;Gulsum Askarova ,&nbsp;Fatima Suleimenova ,&nbsp;Nabras Al-Mahrami ,&nbsp;Prasanta Kumar Parida","doi":"10.1016/j.jgeb.2024.100439","DOIUrl":"10.1016/j.jgeb.2024.100439","url":null,"abstract":"<div><div>The coronavirus that causes serious acute respiratory syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a major problem in public health and biomedicine. Even if there is no cure for it, the infection is still progressing naturally, and the only time that optimal treatment choices, such as doxycycline, work is at the beginning of the infection. Our project is structured into two critical parts: the first focuses on the identification of potential drug targets, and the second on vaccine design, both aimed at exploring new ways to treat the disease. Initially, cytoplasmic proteins identified through subtractive analysis underwent comprehensive evaluation for potential drug targeting, focusing on metabolic pathways, homology prediction, drugability assessment, essentiality, and protein–protein interactions. Subsequently, surface proteins underwent rigorous assessment for allergenicity, antigenicity, physiochemical attributes, conserved regions, protein interactions, and identification of B and T cell epitopes. Molecular docking and immunological simulation analyses were then employed to develop and characterize a multi-epitope vaccine, integrating findings from the aforementioned evaluations. Findings from the study point to six proteins as potential critical therapeutic targets for SARS-CoV-2, each of which is involved in a distinct metabolic process. The reverse vaccinology analysis suggested that the following proteins could be used as vaccine candidates: sp|P05106, sp|O00187, sp|Q9NYK1, sp|P05556, sp|P09958, and sp|Q9HC29. Four multi-epitope vaccine named as SARS-COV-2-, C1, C2, C3, and C4 was designed by utilizing different adjuvants and eighteen B cell overlapped epitopes which were predicted from top ranked protiens. Based on immune simulation study, the vaccine exhibited adequate immune-reactivity and favorable encounters with toll-type receptors (TLR4, TLR8, HLA, etc ACE), Among them the SARS-COV-2-C2 showed best binding affinity of which all receptors. Findings from this study could be a game-changer in the quest to develop a vaccine and medication that effectively combat SARS-CoV-2. It is necessary to do additional experimental analyses, nevertheless.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100439"},"PeriodicalIF":3.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142659012","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}
引用次数: 0
Association of plasma microRNAs with COVID-19 severity and outcome 血浆微RNA与COVID-19严重程度和预后的关系
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2024-11-14 DOI: 10.1016/j.jgeb.2024.100433
Sohair Salem , Randa Lotfy , Noha Eltaweel , Mohamed Elbadry
{"title":"Association of plasma microRNAs with COVID-19 severity and outcome","authors":"Sohair Salem ,&nbsp;Randa Lotfy ,&nbsp;Noha Eltaweel ,&nbsp;Mohamed Elbadry","doi":"10.1016/j.jgeb.2024.100433","DOIUrl":"10.1016/j.jgeb.2024.100433","url":null,"abstract":"<div><h3>Objective</h3><div>As one of the remarkable host responses to SARS-CoV-2 infection, circulating microRNAs (miRNAs) represent important diagnostic and prognostic diseases biomarkers. The study is a step towards highlighting the role of miRNAs in COVID-19 pathogenesis and severity.</div></div><div><h3>Methods</h3><div>In this case-control study, miRCURY LNA miRNA PCR plasma panel (168 miRNAs) was applied and the expression of the altered miRNAs was then analysed by quantitative real time PCR for 120 COVID-19 patients (30 mild, 30 moderate, 30 severe, and 30 critical) and 30 healthy subjects.</div></div><div><h3>Results</h3><div>The initial screening showed that 30 miRNAs displayed altered expression, out of them, only eleven miRNAs (miR-885-5p, miR-141-3p, miR-21-5p, miR-127-3p, miR-99b-5p, let-7d-3p, miR-375, miR-1260a, miR-139-5p, miR-28-5p and miR-34a-5p) were dysregulated in the plasma of COVID-19 patients; all of them were significantly overexpressed. By applying ROC curve analysis, AUC for the eleven miRNAs were ranged from 0.65 to 0.83, and the AUC for the combined miRNAs was 0.93. Ten miRNAs (miR-141-3p, miR-181a-5p, miR-221-3p, miR-223-5p, miR99b-5p, Let-7d-3p, miR-375, miR-199a-5p, miR-139-5p and miR-28-5p) exhibited a significant change in their expression between different severity groups. Patients with positive outcome were found to have increased miR-375 and decreased miR-99b-5p expression levels. Bioinformatic prediction showed that, out of the eleven dysregulated miRNAs, five miRNAs (miR-139-5p, −34a-5p, −28-5p, −21-5p and −885-5p) have the ability to regulate at least two genes related to COVID-19 according to KEGG database.</div></div><div><h3>Conclusion</h3><div>miRNAs are dysregulated in COVID-19 patients and associated with severity degree and patients’ outcome.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"22 4","pages":"Article 100433"},"PeriodicalIF":3.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142659011","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}
引用次数: 0
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