Muhammad Naveed, Muhammad Aqib Shabbir, Tariq Aziz, Hafiz Muhammad Hurraira, Sayyeda Fatima Zaidi, Ramsha Athar, Hassan Anwer Chattha, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari
{"title":"CRISPR-Cas9 guided rna based model for the treatment of Amyotrophic Lateral Sclerosis: A progressive neurodegenerative disorder.","authors":"Muhammad Naveed, Muhammad Aqib Shabbir, Tariq Aziz, Hafiz Muhammad Hurraira, Sayyeda Fatima Zaidi, Ramsha Athar, Hassan Anwer Chattha, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari","doi":"10.18388/abp.2020_6789","DOIUrl":"10.18388/abp.2020_6789","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to the degeneration of motor neurons and the weakening of muscles. Despite extensive research efforts, there is currently no cure for ALS and existing treatments only address its symptoms. To address this unmet medical need, genome editing technologies, such as CRISPR-Cas9, have emerged as a promising solution for the development of new treatments for ALS. Studies have shown that CRISPR-Cas9-guided RNAs have the potential to provide accurate and effective silencing in the genetic disease of ALS. Results have demonstrated a 67% on-target score and a 98% off-target score with GC content within the range of 40-60%. This is further validated by the correlation between the gRNA's structural accuracy and the minimum free energy. The use of CRISPR-Cas9 provides a unique opportunity to target this disease at the molecular level, offering hope for the development of a more effective treatment. In silico and computational therapeutic approaches for ALS suggest that the CRISPR-Cas9 protein holds promise as a future treatment candidate. The CRISPR mechanism and the specificity of gRNA provide a novel therapeutic approach for this genetic disease, offering new hope to those affected by ALS. This study highlights the potential of CRISPR-Cas9 as a promising solution for the development of new treatments for ALS. Further research is required to validate these findings in preclinical and clinical trials and to establish the safety and efficacy of this approach in the treatment of ALS.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":" ","pages":"643-653"},"PeriodicalIF":1.7,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10541285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circ_PWWP2A promotes lung fibroblast proliferation and fibrosis via the miR-27b-3p/GATA3 axis, thereby aggravating idiopathic pulmonary fibrosis.","authors":"LiQing Su, Ying Nian, TianJi Zhu","doi":"10.18388/abp.2020_6459","DOIUrl":"10.18388/abp.2020_6459","url":null,"abstract":"<p><strong>Objective: </strong>This paper was to investigate the effect of circ_PWWP2A-mediated miR-27b-3p/GATA3 axis on idiopathic pulmonary fibrosis (IPF).</p><p><strong>Methods: </strong>circ_PWWP2A expression in lung fibroblasts MLg2908 induced by different concentrations of TGF-β was detected. The relationship between circ_PWWP2A or GATA3 and miR-27b-3p was analyzed by RNA immunoprecipitation and dual-luciferin reporter assay. The proliferation of MLg2908 cells was determined by MTT. GATA3, α-SMA, Collagen-I, and Collagen-III in cells were detected by RT-qPCR and Western blot. The rat model of IPF induced by bleomycin (BLM) was constructed and treated with circ_PWWP2A siRNA injection. HE and Masson staining were of utility to evaluate the pathological conditions of rat lung tissue, and circ_PWWP2A, miR-27b-3p, and GATA3 levels in lung tissues were detected by RT-qPCR. Immunohistochemistry was used to detect the staining of α-SMA, collagen I, and collagen III in the lung tissues of rats.</p><p><strong>Results: </strong>circ_PWWP2A in MLg2908 cells induced by TGF-β decreased in a concentration-dependent manner. MLg2908 cells transfected with circ_PWWP2A siRNA were induced by 5 ng/ml TGF-β, decreasing circ_PWWP2A and GATA3 levels, increasing miR-27b-3p expression, and suppressing cell proliferation. The targeting relationship between circ_PWWP2A and miR-27b-3p, as well as miR-27b-3p and GATA3, was confirmed. Depleting miR-27b-3p reduced the inhibitory effect of circ_PWWP2A down-regulation on the proliferation of TGF-β-treated MLg2908 cells, accompanied by increased expression of α-SMA, Collagen 1, and Collagen 3, and increased expression of GATA3. The in vivo results showed that BLM-induced fibrosis in rat lung tissue was obvious, accompanied by increased expression of circ_PWWP2A and GATA3, decreased expression of miR-27b-3p, and deepened staining of α-SMA, collagen I, and collagen III, but circ_PWWP2A siRNA could improve these phenomena.</p><p><strong>Conclusion: </strong>Silencing circ_PWWP2A can inhibit the proliferation of lung fibroblasts induced by TGF-β through the miR-27b-3p/GATA3 axis, and reduce BLM-induced pulmonary fibrosis in rats, which may be a potential therapeutic target for IPF.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":" ","pages":"525-532"},"PeriodicalIF":1.7,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10167421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nageen Hussain, Mohsin Mumtaz, Mohammad Adil, Abad Ali Nadeem, Abid Sarwar, Tariq Aziz, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari, Mousa Essa Alharbi
{"title":"Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA.","authors":"Nageen Hussain, Mohsin Mumtaz, Mohammad Adil, Abad Ali Nadeem, Abid Sarwar, Tariq Aziz, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari, Mousa Essa Alharbi","doi":"10.18388/abp.2020_6654","DOIUrl":"10.18388/abp.2020_6654","url":null,"abstract":"<p><p>Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":" ","pages":"591-598"},"PeriodicalIF":1.7,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10217817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lina Elsalem, Ahmad Al Shatnawi, Mahmoud A Alfaqih, Ayat Alshoh, Saddam Al Demour, Ali Al-Daghmin, Omar Halalsheh, Khalid Kheirallah, Mamoun Ahram
{"title":"Discovery of a novel genetic variant in the N-acetyltransferase2 (NAT2) gene that is associated with bladder cancer risk.","authors":"Lina Elsalem, Ahmad Al Shatnawi, Mahmoud A Alfaqih, Ayat Alshoh, Saddam Al Demour, Ali Al-Daghmin, Omar Halalsheh, Khalid Kheirallah, Mamoun Ahram","doi":"10.18388/abp.2020_6590","DOIUrl":"10.18388/abp.2020_6590","url":null,"abstract":"<p><p>Smoking is a main risk factor for bladder cancer (BC). NAT2 is a drug-metabolizing enzyme that catalyses the detoxification of many xenobiotics and carcinogens. Single nucleotide polymorphism (SNP) in NAT2 results in different acetylation phenotypes (fast, intermediate or slow). Certain NAT2 SNPs were associated with BC and/or modified the association of BC with smoking. However, limited evidence is available among BC patients or smokers from Jordan. This study aimed to discover novel SNPs in NAT2 and to assess the association with BC. This was a case-control study among 120 BC patients and 120 controls. Amplification of a 446 bp fragment of NAT2 encoding the N-catalytic domain was conducted using a polymerase chain reaction. Gene sequencing was done using Sanger-based technology. A total of 40 SNPs were detected. Two variants were significantly associated with BC (p<0.05); namely a novel c.87G>A and the reported c.341T>C. Regarding c.87G>A, genotype distribution was significantly associated with BC and subgroup analysis confirmed that this was significant in both smokers (p=0.007) and non-smokers (p=0.001). Regression subgroup analysis suggested GA as a risk factor among smokers (AOR= 2.356). The frequencies of TC and CC genotypes of c.341T>C were significantly higher in BC (p<0.05). This was statistically significant among smokers only (p=0.044), upon subgroup analysis. Multivariate analysis showed that subjects with TC genotype are 6.15 more likely to develop BC and regression subgroup analysis revealed TC as a risk factor among smokers (AOR=5.47). This is the first study from Jordan to report the association of smoking and two NAT2 variants with BC. The data supports the use of GA and TC genotypes of the novel c.87G>A and the reported c.341T>C SNPs, respectively as potential biomarkers of BC, particularly among smokers. Future investigations with a larger population are required to support our findings.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":" ","pages":"575-582"},"PeriodicalIF":1.7,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10025806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejaz Ahmad, Muhammad Jahangeer, Zahid Mahmood Akhtar, Tariq Aziz, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari, Nadeem Irfan Bukhari
{"title":"Characterization and gastroprotective effects of Rosa brunonii Lindl. fruit on gastric mucosal injury in experimental rats - A preliminary study.","authors":"Ejaz Ahmad, Muhammad Jahangeer, Zahid Mahmood Akhtar, Tariq Aziz, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari, Nadeem Irfan Bukhari","doi":"10.18388/abp.2020_6772","DOIUrl":"10.18388/abp.2020_6772","url":null,"abstract":"<p><p>Gastric ulcer is the most prevalent disorder affecting a large population. Rosa brunonii Lindl. fruit (RBF) has traditionally been used to treat stomach pains. Therefore, the current work aimed to isolate, characterize, and investigate the gastro-protective effect of Rosa brunonii Lindl. fruit chloroform extract (RBFCE) against ethanol-induced gastric ulcers in rats. Quercetin 3-O-glucoside (QUE-G) was isolated and characterized by modern spectroscopic techniques. RBFCE was orally administered at 250 mg/kg, 500 mg/kg, and 750 mg/kg doses for ten days. Gastric ulcer was induced by a single dose of absolute ethanol (5 ml/kg) on the last day of the study. Histological changes were calculated, along with ulcer inhibition and the ulcer index (UI). Gastric juice volume, pH, acidity, mucus content, and protein content were evaluated to understand the mechanism underlying its gastroprotective effect. Omeprazole (OMP) was used as the positive control. RBFCE at a dose of 750 mg/kg significantly (p<0.01) reduced the UI (3.54) and increased the protection rate (67.63%) compared to the negative (ulcer) control group. Treatment with RBFCE in a dose-dependent manner increased the gastric pH, mucus content, and total protein while decreasing gastric juice volume and total acidity. Histopathological studies showed severe gastric mucosal injury and edema in ulcer control animals compared to extract-treated groups. This study demonstrated that oral administration of RBFCE possesses a significant gastroprotective effect due to its anti-secretory and cytoprotective mechanisms. Our findings support the traditional use of RBF to treat the gastric ulcer.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":" ","pages":"633-641"},"PeriodicalIF":1.7,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circ-POLA2-mediated miR-138-5p/SEMA4C axis affects colon cancer cell activities.","authors":"YanDong Huang, QingYang Bai, HongBo Yu, YanRu Li, Hao Lu, HuiMin Kang, XueWei Shi, Kai Feng","doi":"10.18388/abp.2020_6457","DOIUrl":"10.18388/abp.2020_6457","url":null,"abstract":"<p><p>This study aimed to investigate the mechanism of circ-POLA2 in colon cancer (CC). Circ-POLA2, miR-138-5p, and SEMA4C levels in CC tissues and cells were recorded. The influences mediated by circ-POLA2, miR-138-5p or SEMA4C on cell proliferation, migration, invasion, and apoptosis were determined. The feedback loop of circ-POLA2/miR-138-5p/SEMA4C was surveyed. As measured, circ-POLA2 and SEMA4C were highly expressed, while miR-138-5p was poorly expressed. Meanwhile, circ-POLA2 could mediate SEMA4C through miR-138-5p targeting. Circ-POLA2 knockdown caused the blockade for cell activities, but this effect was alleviated by miR-138-5p inhibition or SEMA4C overexpression. Overall, circ-POLA2 is tumorigenic for CC through miR-138-5p/SEMA4C axis, which may provide a promising molecular target for CC therapy.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":" ","pages":"517-523"},"PeriodicalIF":1.7,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10025802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Yan, Tian Wen Long, Xi Niu, Jia Fu Wang, Sheng Li
{"title":"MiR-96-5p is involved in permethrin-promoted proliferation and migration of breast cancer cells.","authors":"Yi Yan, Tian Wen Long, Xi Niu, Jia Fu Wang, Sheng Li","doi":"10.18388/abp.2020_6533","DOIUrl":"10.18388/abp.2020_6533","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are major players in cellular responses to xenobiotic compounds and toxins. However, the role of miRNAs in pyrethroid pesticide-induced cancer progression remains unclear. This study aimed to investigate the function of miR-96-5p in permethrin-induced proliferation and migration in breast cancer cells. In our study, the expression of miR-96-5p was upregulated in permethrin-treated MCF-7 cells. MiR-96-5p promoted MCF-7 cell proliferation and migration, accompanied bychanges in the expression of proteins involved in cell proliferation, migration, and apoptosis. Homeobox A5 (HOXA5) was identified as a direct target of miR-96-5p. HOXA5 silencing had the opposite effects with miR-96-5p inhibition. In conclusion, these results suggest that miR-96-5p is involved in permethrin-promoted proliferation and migration of breast cancer cells by targeting HOXA5.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":" ","pages":"561-566"},"PeriodicalIF":1.7,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10025804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irena Roterman, Katarzyna Stapor, Dawid Dułak, Leszek Konieczny
{"title":"Secondary structure in polymorphic forms of alpha-synuclein amyloids.","authors":"Irena Roterman, Katarzyna Stapor, Dawid Dułak, Leszek Konieczny","doi":"10.18388/abp.2020_6788","DOIUrl":"https://doi.org/10.18388/abp.2020_6788","url":null,"abstract":"<p><p>Numerous Alpha-synuclein amyloid structures available in PDB enable their comparative analysis. They are all characterized by a flat structure of each individual chain with an extensive network of inter-chain hydrogen bonds. The identification of such amyloid fibril structures requires determining the special conditions imposed on the torsion angles. Such conditions have already been formulated by the Authors resulting in the model of idealised amyloid. Here, we investigate the fit of this model in the group of A-Syn amyloid fibrils. We identify and describe the characteristic supersecondary structures in amyloids. Generally, the amyloid transformation is suggested to be the 3D to 2D transformation engaging mostly the loops linking Beta-structural fragments. The loop structure introducing the 3D organisation of Beta-sheet change to flat form (2D) introduces the mutual reorientation of Beta-strands enabling the large-scale H-bonds generation with the water molecules. Based on the model of idealised amyloid we postulate the hypothesis for amyloid fibril formation based on the shaking, an experimental procedure producing the amyloids.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":"70 2","pages":"435-445"},"PeriodicalIF":1.7,"publicationDate":"2023-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benish Rauf, Sobia Alyasi, Naureen Zahra, Sohail Ahmad, Abid Sarwar, Tariq Aziz, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari
{"title":"Evaluating the influence of Aloe barbadensis extracts on edema induced changes in C-reactive protein and interleukin-6 in albino rats through in vivo and in silico approaches.","authors":"Benish Rauf, Sobia Alyasi, Naureen Zahra, Sohail Ahmad, Abid Sarwar, Tariq Aziz, Metab Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari","doi":"10.18388/abp.2020_6705","DOIUrl":"https://doi.org/10.18388/abp.2020_6705","url":null,"abstract":"<p><p>The current study investigated the in-vivo and in-silico anti-inflammatory effect of Aloe barbadensis in edema induced rat and its blood biomarkers. 60 albino rats (160-200 g) were divided into 4 groups. The 1st group (control) comprised of 6 rats that were treated with saline. The 2nd group (standard) comprised of 6 rats that were treated with diclofenac. The 3rd and 4th experimental groups consisted of 48 rats, treated with A. barbadensis gel ethanolic and aqueous extracts respectively at doses of 50, 100, 200 and 400 mg/kg. According to paw sizes, groups III and IV showed 51% and 46% inhibition respectively at the 5th hour, as compared to group II with 61% inhibition. Correlation was negative between biomarkers in group III, while, positive in group IV. Blood samples were collected; C-reactive protein and interleukin-6 were measured using commercially available ELISA kits. Similarly, biomarkers showed significant effect in dose-dependent manner. In molecular docking, for CRP both ligands aloe emodin and emodin showed -7.5 kcal/mol binding energy as compared to diclofenac with -7.0 kcal/mol. For IL-1beta, both ligands showed -4.7 kcal/mol binding energy as compared to diclofenac -4.4 kcal/mol. Hence, we concluded that A. barbadensis extracts can be used as an effective drug for managing inflammation.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":"70 2","pages":"425-433"},"PeriodicalIF":1.7,"publicationDate":"2023-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9661351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Naveed, Urooj Ali, Tariq Aziz, Muhammad Junaid Rasool, Adil Ijaz, Metab Alharbi, Mousa Essa Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari
{"title":"A reverse vaccinology approach to design an mRNA-based vaccine to provoke a robust immune response against HIV-1.","authors":"Muhammad Naveed, Urooj Ali, Tariq Aziz, Muhammad Junaid Rasool, Adil Ijaz, Metab Alharbi, Mousa Essa Alharbi, Abdulrahman Alshammari, Abdullah F Alasmari","doi":"10.18388/abp.2020_6696","DOIUrl":"10.18388/abp.2020_6696","url":null,"abstract":"<p><p>There have been substantial advances in HIV research over the past three decades, but we are still far from our goal of eliminating HIV-1 infection entirely. Numerous ever-evolving antigens are produced as a result of HIV-1's genetic variability. Developing an effective vaccination is challenging because of the structural properties of the viral envelope glycoprotein that obscure conserved receptor-binding sites and the presence of carbohydrate moieties that prevent antibodies from reaching potential epitopes. To work on an HIV-specific vaccine, this study identified 5 HIV-surface proteins, from the literature, to screen potential epitopes and construct an mRNA vaccine. A wide range of immunological-informatics techniques were utilized to develop a construct that efficiently stimulated cellular and humoral immune responses. The vaccine was produced with 31 epitopes, a TLR4 agonist termed RpfE that acts as an adjuvant, secretion boosters, subcellular trafficking structures, and linkers. It was determined that this suggested vaccine would cover 98.9 percent of the population, making it widely available. We, furthermore, carried out an immunological simulation of the vaccine illustrating the active and stable responses from innate and adaptive immune cells, the memory cells remained active for up to 350 days after vaccine injection, whereas the antigen was excreted from the body within 24 hours. Docking performed with TLR-4 and TLR-3 showed significant interaction with -11.9kcal/mol and -18.2kcal/mol-1 respectively. Molecular dynamics simulations further validated the vaccine's stability, with a dissociation constant of 1.7E-11 for the TLR3-vaccine complex and 5.8E-11 for the TLR4-vaccine complex. Lastly, codon optimization was carried out to guarantee that the designed mRNA construct would be translated into the host successfully. This vaccine adaptation, if tested in-vitro, would be efficacious and potent as predicted.</p>","PeriodicalId":6984,"journal":{"name":"Acta biochimica Polonica","volume":"70 2","pages":"407-418"},"PeriodicalIF":1.7,"publicationDate":"2023-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}