Molecular Biology Research Communications最新文献_第2页

Investigation methylation status of tumor suppressor gene NR4A1 and NR4A3 and frequency of rs1569686 polymorphism of DNMT3B gene in patients with acute myeloid leukemia. 研究急性髓性白血病患者肿瘤抑制基因NR4A1、NR4A3甲基化状况及DNMT3B基因rs1569686多态性频率。

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2024.51563.2058

Baharan Rahmani, Shahrbano Rostami, Yousef Mortazavi, Mohammad Soleiman Soltanpour

{"title":"Investigation methylation status of tumor suppressor gene NR4A1 and NR4A3 and frequency of rs1569686 polymorphism of DNMT3B gene in patients with acute myeloid leukemia.","authors":"Baharan Rahmani, Shahrbano Rostami, Yousef Mortazavi, Mohammad Soleiman Soltanpour","doi":"10.22099/mbrc.2024.51563.2058","DOIUrl":"https://doi.org/10.22099/mbrc.2024.51563.2058","url":null,"abstract":"Acute myeloid leukemia (AML) is the most frequent type of leukemia among adults. Investigating AML heterogeneity based on DNA methylation can improve clinical diagnosis and prognosis. This study was conducted to investigate NR4A1 and NR4A3 gene methylation in fifty newly diagnosed AML patients and fifty healthy controls using Methyl specific PCR (MSP). The frequency of the rs1569686 in the DNMT3B was also determined by Tetra primer ARMS PCR. Also, the association between methylation of studied genes and some prognostic marker including mutation of FLT3 and NPM genes, as well as some hematological factors of patients was evaluated. According to the findings, AML patients have a significantly higher prevalence of methylated NR4A1 and NR4A3 genes than those without AML. AML patients with un-methylated NR4A3 had significantly higher frequency of FLT-ITD positivity than AML patients with methylated NR4A3. Also, there was no significant association between rs1569686 and AML. Finally, the distribution of different genotypes of rs1569686 between AML patients with and without methylation in NR4A1 and NR4A3 did not show any significant association. The results found that NR4A1 and NR4A3 were hyper-methylated in AML patients. However, rs1569686 polymorphism was not a main contributor to methylation status of studied gene. Future studies should consider other mechanisms influencing the role of NR4A1 and NR4A3 hypermethylation in AML.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 2","pages":"149-156"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542610","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 computational analysis of deleterious nsSNPs in PTEN gene for structural and functional insights. PTEN基因中有害非单核苷酸多态性的综合计算分析，以获得结构和功能上的见解。

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2025.52148.2092

Divyanshi Sharma, Harasees Singh, Aryan Arya, Himanshi Choudhary, Pragya Guleria, Sandeep Saini, Chander Jyoti Thakur

{"title":"Comprehensive computational analysis of deleterious nsSNPs in PTEN gene for structural and functional insights.","authors":"Divyanshi Sharma, Harasees Singh, Aryan Arya, Himanshi Choudhary, Pragya Guleria, Sandeep Saini, Chander Jyoti Thakur","doi":"10.22099/mbrc.2025.52148.2092","DOIUrl":"https://doi.org/10.22099/mbrc.2025.52148.2092","url":null,"abstract":"Single nucleotide polymorphisms (SNPs) are pivotal in understanding the genetic basis of complex disorders. Among them, nonsynonymous SNPs (nsSNPs) that alter amino acid sequences can significantly impact protein structure and function. This study focuses on analyzing deleterious nsSNPs in the tumor suppressor gene PTEN (Phosphatase and TENsin Homolog), which plays a central role in regulating the PI3K/Akt signaling pathway and tumorigenesis. Out of 43,855 SNPs in PTEN, 17 deleterious nsSNPs were identified using six computational tools. Protein stability analysis revealed that 15 variants reduce stability, potentially leading to functional impairment. Structural evaluations using HOPE and ConSurf classified mutations into buried structural residues disrupting protein integrity and exposed functional residues affecting molecular interactions. STRING database analysis highlighted PTEN as a central node in an intricate protein network, with deleterious mutations impairing critical interactions with partners such as PIK3CA, AKT1, and TP53. Secondary structure analysis revealed distinct structural deviations, particularly for G129E, which exhibited the most pronounced destabilization. Molecular dynamics simulations confirmed stability variations across mutants, with G129E exhibiting greater instability. This comprehensive analysis enhances understanding of PTEN nsSNP impacts, offering insights for therapeutic interventions and future experimental validation.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 3","pages":"219-239"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064239","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 CRISPR-HITI strategy approach to improve CHO cell viability by modifying the 3'UTR of Caspase 8 Associated Protein 2. 通过修饰Caspase 8相关蛋白2的3'UTR提高CHO细胞活力的CRISPR-HITI策略方法

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2024.50513.2000

Soofia Sorourian, Abbas Behzad-Behbahani, Mohsen Forouzanfar, Mojtaba Jafarinia, Fatemeh Safari

{"title":"A CRISPR-HITI strategy approach to improve CHO cell viability by modifying the 3'UTR of Caspase 8 Associated Protein 2.","authors":"Soofia Sorourian, Abbas Behzad-Behbahani, Mohsen Forouzanfar, Mojtaba Jafarinia, Fatemeh Safari","doi":"10.22099/mbrc.2024.50513.2000","DOIUrl":"10.22099/mbrc.2024.50513.2000","url":null,"abstract":"Chinese Hamster Ovary (CHO) cells are essential in biopharmaceutical manufacturing. Scientists use CRISPR to enhance productivity. mRNAs contain UTRs that regulate gene expression, affecting protein abundance. Targeting these regions creates desirable knockout cells. The Caspase 8 Associated Protein 2 (CASP8AP2) gene is a promising target for improving host cell viability. This study used the CRISPR-Homology-Independent Targeted Integration (HITI) strategy to modify the 3'UTR region of the CASP8AP2 gene in CHO cells. The aim was to evaluate the effects of CASP8AP2 silencing on cell proliferation, viability, apoptosis, and the cell cycle. CASP8AP2 silencing was assessed post-modification by extracting genomic DNA from modified and unmodified CHO cells, followed by PCR and sequencing to confirm deletions. Cell proliferation and viability were measured using MTT assays, and cell cycle analysis was performed via flow cytometry. Apoptosis was evaluated through Annexin V/PE staining and flow cytometry, with apoptosis resistance assessed by determining the IC50 of sodium butyrate. Results showed CASP8AP2 deletion did not affect cell proliferation or the cell cycle but improved CHO cell viability and increased resistance to apoptosis. The IC50 for sodium butyrate was higher in CASP8AP2 knockout cells (7.84 mM) compared to native cells (3.43 mM), indicating enhanced apoptosis resistance. This study highlights CASP8AP2's role in apoptosis regulation without impacting cell proliferation or the cell cycle. CASP8AP2 deletion enhances viability and resistance to apoptosis, suggesting it as a target for improving recombinant protein production. Further research is needed to elucidate the molecular mechanisms and develop therapeutic strategies based on this approach.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 1","pages":"15-26"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915362","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

Prediction the functional impacts of highly deleterious non-synonymous variants of TSGA10 gene. 预测TSGA10基因高度有害非同义变异体的功能影响。

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2024.49991.1977

Zeinab Jamali, Mahsa Zargar, Mohammad Hossein Modarressi

{"title":"Prediction the functional impacts of highly deleterious non-synonymous variants of TSGA10 gene.","authors":"Zeinab Jamali, Mahsa Zargar, Mohammad Hossein Modarressi","doi":"10.22099/mbrc.2024.49991.1977","DOIUrl":"10.22099/mbrc.2024.49991.1977","url":null,"abstract":"Testis specific gene antigen 10 (TSGA10) is a protein which has roles in spermatogenesis and cancers so that deletion or mutation in the TSGA10 gene resulted in non-obstructive infertility and aberrant expression of this protein, was detected in solid tumors and leukemia. Despite the crucial roles of TSGA10 in tumorigenesis and infertility, yet it is not obvious how various nsSNPs of its gene impress the structure and function of the TSGA10. Therefore, it is worthwhile to investigate the potential highly deleterious nsSNPs by several in-silico tools before launching costly experimental approaches. In the current study, we employed several different machine learning algorithms in a two-step screening procedure to analyze single nucleotide substitutions of TSGA10 gene. Prediction tools were included SIFT, PROVEAN, PolyPhen-2, SNAP2, SNPs & GO, PhD-SNP for the first step and the second step included predictive tools such as I-mutant 3.0, MUpro, SNPeffect 4.0 (LIMBO, WALTZ, TANGO, FoldX), MutationTaster and CADD. Also, the 3D models of significantly damaging variants were built by Phyre2. The results elucidated 15 amino acid alterations as the most deleterious ones. Among these S563P, E578K, Q580P, R638L, R638C, R638G, R638S, L648R, R649C, R649H were located in a domain which is approved to has interaction with the HIF1-A protein and D62Y, R105G, D106V and D111Y were located on phosphodiesterase domain. In sum, these predicted mutations significantly influence the function of TSGA10 and they could be used for precise study of this protein in infertility and cancer experimental investigations.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 1","pages":"47-58"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915427","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

Isolation and characterization of thermotolerant hydrocarbon degrading bacteria which sustained the activity at extreme salinity and high osmotic conditions. 分离耐高温碳氢化合物降解细菌并确定其特征，这些细菌在极端盐度和高渗透条件下仍能保持活性。

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2024.49747.1946

Saman Hosseini, Rouhallah Sharifi, Alireza Habibi, Ali Beheshti-AleAgha

{"title":"Isolation and characterization of thermotolerant hydrocarbon degrading bacteria which sustained the activity at extreme salinity and high osmotic conditions.","authors":"Saman Hosseini, Rouhallah Sharifi, Alireza Habibi, Ali Beheshti-AleAgha","doi":"10.22099/mbrc.2024.49747.1946","DOIUrl":"10.22099/mbrc.2024.49747.1946","url":null,"abstract":"The bioremediation method is considered an economical and environmentally friendly strategy for the remediation of oil-contaminated soils. However, some oil field areas have extreme environmental conditions that make it difficult to establish microbes for bioreme-diation. In this study, bacteria were isolated from oil-contaminated soils of the Dehloran oil fields, which have very harsh soil and weather conditions. Soil samples were collected from two highly contaminated mud pits. The petroleum content and physicochemical characteristics of the soil were investigated. Soil samples pollution were about 8%, sandy and alkaline, and their EC reached up to 125.6 ds/m in some samples. The isolated bacteria were screened according to their ability to grow on the M9 mineral medium containing crude oil as the sole carbon source. Moreover, their physiological characteristics in diesel degradation were investigated. The phenotypic, biochemical, and molecular characteristics of selected isolates and their stability under extreme conditions such as drought, salinity and high temperatures were investigated. Two isolates NC39 and NB391 showed the highest ability in diesel degradation. The results of 16SrRNA sequencing showed that NC39 isolate had 98% similarity to Pseudomonas sp. and isolate NB391 belonged to Pantoea agglomerans with 99% similarity. These two isolates showed a high ability to tolerate high salinity (10%), temperature (50°C), and drought (-0.73 MPa) stress. Exploiting these extremophile strains is a promising tool in the bioremediation of oil-contaminated soils in extreme environments.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 1","pages":"37-46"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915420","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

HIV-1 reverse transcriptase subtyping revealed CRF35-AD as a current subtype in the northeast of Iran. HIV-1逆转录酶亚型显示CRF35-AD是伊朗东北部的一种当前亚型。

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2025.52193.2089

Zahra Mazaheri, Masoud Youssefi

引用次数: 0

Expression patterns of circRFX3 and miR-587 in colorectal cancer patients. circRFX3和miR-587在结直肠癌患者中的表达模式

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2025.52016.2080

Samaneh Najafi, Zivar Salehi, Farhad Mashayekhi, Hamid Saidi-Saedi

{"title":"Expression patterns of circRFX3 and miR-587 in colorectal cancer patients.","authors":"Samaneh Najafi, Zivar Salehi, Farhad Mashayekhi, Hamid Saidi-Saedi","doi":"10.22099/mbrc.2025.52016.2080","DOIUrl":"https://doi.org/10.22099/mbrc.2025.52016.2080","url":null,"abstract":"Circular RNAs (circRNAs) are non-coding, single-stranded RNAs considered by their closed-loop structures. Research has established a connection between circRNAs and cancer progression. The objective of this project was to evaluate the expression levels of a newly discovered circRNA, circRFX3 (hsa_circRFX3_003), along with its target gene, miR-587. The study involved 60 patients diagnosed with Colorectal cancer (CRC) and 60 healthy individuals as controls. Total RNA was extracted from blood samples, converted into cDNA, and analyzed using qRT-PCR. The findings revealed an up-regulation of miR-587 and a down-regulation of circRFX3 in the blood samples of CRC patients. An inverse relationship was observed between the levels of miR-587 and circRFX3; however, there was no significant difference in circRFX3 expression levels between stages I+II and stages III+IV. The levels of miR-587 expression were linked to tumor size and location. Both circRFX3 and miR-587 play significant roles in the pathophysiology of CRC; however, additional research is necessary to elucidate their specific contributions to CRC development.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 3","pages":"243-248"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003338","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

Expressing red fluorescent protein on the surface of Escherichia coli using C-terminal domain of autotransporters. 利用自体转运体的 C 端结构域在大肠杆菌表面表达红色荧光蛋白。

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2024.49860.1956

Khoi-Nguyen Le-Hoang, Thanh-Tan Nguyen, Hieu Tran-Van

{"title":"Expressing red fluorescent protein on the surface of Escherichia coli using C-terminal domain of autotransporters.","authors":"Khoi-Nguyen Le-Hoang, Thanh-Tan Nguyen, Hieu Tran-Van","doi":"10.22099/mbrc.2024.49860.1956","DOIUrl":"10.22099/mbrc.2024.49860.1956","url":null,"abstract":"The Type V secretion system, or \"autotransporter\", is a secretion system that enables bacteria to directly export proteins from the cell interior to the extracellular membrane. mCherry is a second-generation monomeric red fluorescent protein that has an improvement in photostability compared to the first generation of RFP. In this research, we conducted the fusion of the mRFP into the C-terminal domain of EhaA - the translocation domain of the autotransporter protein transport system - to investigate the expression of mRFP on the surface of Escherichia coli , a model organism commonly utilized in recombinant protein research. The induction of the mRFP-EhaA C-terminal domain complex expression was achieved using isopropyl β-D-1-thiogalactopyranoside (IPTG) and confirmed through SDS-PAGE stained with Coomassie Brilliant Blue and Western blotting using anti-6X His tag antibodies. The surface expression of the mRFP-EhaA C-terminal complex protein was validated through the fluorescent properties of mRFP and further confirmed using fluorescent microscopy. This study laid the groundwork for surface expression on cost-effective Gram-negative bacteria, E. coli.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 1","pages":"31-35"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915404","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

Dysregulated LINC01133 expression in laryngeal carcinoma: Prognostic implications and predicted ceRNA interactome. 喉癌中LINC01133表达异常：预后意义和预测ceRNA相互作用组。

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2024.50390.1996

Masoumeh Razipour, Zeinab Jamali, Saeed Sohrabpour, Farrokh Heidari, Maryam Lotfi, Elham Ghadami, Maryam Abtin, Mohaddese Maghsudlu, Leyla Sahebi, Abbas Shakoori

{"title":"Dysregulated LINC01133 expression in laryngeal carcinoma: Prognostic implications and predicted ceRNA interactome.","authors":"Masoumeh Razipour, Zeinab Jamali, Saeed Sohrabpour, Farrokh Heidari, Maryam Lotfi, Elham Ghadami, Maryam Abtin, Mohaddese Maghsudlu, Leyla Sahebi, Abbas Shakoori","doi":"10.22099/mbrc.2024.50390.1996","DOIUrl":"10.22099/mbrc.2024.50390.1996","url":null,"abstract":"Long non-coding RNAs (lncRNAs) have recently emerged as critical regulators of oncogenic or tumor-suppressive pathways in human cancers. LINC01133 is a lncRNA that has exhibited dichotomous roles in various malignancies but to the best of our knowledge, the role of LINC01133 in laryngeal squamous cell carcinoma (LSCC) has not been previously investigated. This study aimed to investigate the expression, clinical significance, and potential functions of the LINC01133 in LSCC. Integrative bioinformatics analysis of sequencing data obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed LINC01133 as a differentially expressed lncRNA in head and neck/laryngeal cancers. Experimental validation via quantitative real-time PCR in 41 pairs of stage III and IV LSCC tissues and normal tissues adjacent to the tumor (NAT) demonstrated significant downregulation of LINC01133 in tumors (p<0.0001). Decreased LINC01133 expression associated with advanced tumor stage (p=0.0206) and lymph node metastasis (p=0.0203). The receiver operating characteristic analysis indicated potential diagnostic utility (AUC=0.7115, p=0.001). Bioinformatic predictions and literature mining suggested two potential competing endogenous RNA (ceRNA) mechanisms whereby LINC01133 may act as a tumor suppressor by sponging miR-205-5p to derepress the leucine-rich repeat kinase 2 (LRRK2) and androgen receptor, leading to dysregulation of cancer-related signaling cascades. This study provides initial evidence that loss of lncRNA LINC01133 expression may promote LSCC tumorigenesis, possibly by dysregulating microRNA interactions. Further verification of its regulatory mechanisms and diagnostic value is warranted.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 1","pages":"93-107"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915372","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

Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8. 天然产物通过关键中介蛋白ORF8对SARS-CoV-2的非刺突蛋白抑制作用

IF 1.5

Molecular Biology Research Communications Pub Date : 2025-01-01 DOI: 10.22099/mbrc.2024.50245.2001

Mostafa Bagheri-Far, Mohammad Assadizadeh, Maryam Azimzadeh-Irani, Mohammad Yaghoubi-Avini, Seyed Massoud Hosseini

{"title":"Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8.","authors":"Mostafa Bagheri-Far, Mohammad Assadizadeh, Maryam Azimzadeh-Irani, Mohammad Yaghoubi-Avini, Seyed Massoud Hosseini","doi":"10.22099/mbrc.2024.50245.2001","DOIUrl":"10.22099/mbrc.2024.50245.2001","url":null,"abstract":"The recent pernicious COVID-19 pandemic is caused by SARS-CoV-2. While most therapeutic strategies have focused on the viral spike protein, Open Reading Frame 8 (ORF8) plays a critical role in causing the severity of the disease. Nonetheless, there still needs to be more information on the ORF8 binding epitopes and their appropriate safe inhibitors. Herein, the protein binding sites were detected through comprehensive structural analyses. The validation of the binding sites was investigated through protein conservation analysis and blind docking. The potential natural product (NP) inhibitors were selected based on a structure-function approach. The solo and combined inhibition functions of these NPs were examined through molecular docking studies. Two binding epitopes were identified, one between the ORF8 monomers (DGBM) and the other on the surface (Gal1-Like). E92 was predicted to be pivotal for DGBM, and R101 for Gal1-like, which was then confirmed through molecular dockings. The inhibitory effects of selected phytochemical (Artemisinin), bacterial (Ivermectin), and native-liken (DEG-168) NPs were compared with the Remdesivir. Selected NPs showed solo- and co-functionality against Remdesivir to inhibit functional regions of the ORF8 structure. The DGBM is highly engaged in capturing the NPs. Additionally, the co-functionality study of NPs showed that the Ivermectin-DEG168 combination has the strongest mechanism for inhibiting all the predicted binding sites. Ivermectin can interfere with ORF8-MHC-I interaction through inhibition of A51 and F120. Two new binding sites on this non-infusion protein structure were introduced using a combination of approaches. Additionally, three safe and effective were found to inhibit these binding sites.","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"14 1","pages":"73-91"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915424","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