Molekulyarnaya Biologiya最新文献

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[Multi-Omic Rejuvenation: A New Strategy for Lifespan Extension]. [多基因组再生:延长寿命的新策略]。
Molekulyarnaya Biologiya Pub Date : 2024-09-01 DOI: 10.31857/S0026898424050013, EDN: HUVYAW
O Y Rybina, E G Pasyukova
{"title":"[Multi-Omic Rejuvenation: A New Strategy for Lifespan Extension].","authors":"O Y Rybina, E G Pasyukova","doi":"10.31857/S0026898424050013, EDN: HUVYAW","DOIUrl":"10.31857/S0026898424050013, EDN: HUVYAW","url":null,"abstract":"<p><p>Various age-related disorders accumulate during aging, causing a decline in tissue and organ function, raising the risk of disease development, and leading to death. Age-related phenotypes are tightly related to an increase in coordinated, progressive changes in the transcriptome, proteome, metabolome, microbiome, and epigenome. Age-dependent modifications of the transcriptome, caused by changes in epigenetic, transcriptional, and post-transcriptional regulation of gene expression, lead to the accumulation of age-related changes in the proteome and metabolome. In turn, dynamic changes in the microbiota during aging also affect gene expression and thus lead to age-related changes in the proteome and metabolome. Recent studies have shown that multi-omic rejuvenation technologies decrease age-related disorders and extend longevity. For example, the short-term induction of the expression of transcription factors that ensure the reprogramming of somatic cells into pluripotent stem cells is accompanied by the restoration of the DNA methylation pattern and transcriptome expression profile characteristic of younger tissues, resulting in an increased lifespan. In this review, we discuss existing multi-omic rejuvenation technologies and the prospects for extending and improving life.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 5","pages":"684-693"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Spatial Organization of Chromatin of the KLF5 Gene Promoter Region in Pancreatic Ductal Adenocarcinoma Cells]. [胰腺导管腺癌细胞KLF5基因启动子区域染色质的空间组织]。
Molekulyarnaya Biologiya Pub Date : 2024-09-01 DOI: 10.31857/S0026898424050069, EDN: HUOYYD
M V Zinovyeva, L G Nikolaev
{"title":"[Spatial Organization of Chromatin of the KLF5 Gene Promoter Region in Pancreatic Ductal Adenocarcinoma Cells].","authors":"M V Zinovyeva, L G Nikolaev","doi":"10.31857/S0026898424050069, EDN: HUOYYD","DOIUrl":"10.31857/S0026898424050069, EDN: HUOYYD","url":null,"abstract":"<p><p>Pancreatic Ductal AdenoCarcinoma (PDAC) is characterized by a poor prognosis and is poorly amenable to modern therapies. A range of cell cultures reflecting different degrees of tumor differentiation and malignancy can serve as a model of PDAC development. Highly differentiated cells with low malignancy are characterized by increased expression of the KLF5 gene. The KLF5 protein is a vivid representative of multifunctional transcription factors, and its involvement in a variety of cellular processes, particularly in the pathology of various cancers, has been demonstrated. We investigated the spatial organization of chromatin of the regulatory regions of the KLF5 gene using highly differentiated Capan2 PDAC cells with a high level of KLF5 expression and poorly differentiated MIA PaCa2 PDAC cells with a low level of expression of this gene by circular chromosome conformation capture (4C-seq). It was shown that the number and distribution of contacts of the KLF5 regulatory region with other chromatin regions are significantly different for these types of cells; the number of contacts is significantly higher for Capan2 cells. There is a correlation between the expression level of genes close to KLF5 and the intensity of their sequence contacts with the KLF5 regulatory region, indicating that their expression is coordinated, possibly within the transcriptional factory. Capan2 is characterized by a high level of contacts of the KLF5 regulatory region with the gene-free region containing a cluster of PDAC-associated single nucleotide polymorphisms (SNP/InDel). Thus, the total number of contacts of the promoter region of the KLF5 gene and the expression level of most of the surrounding KLF5 genes decrease as the grade of cell malignancy increases.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 5","pages":"756-771"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[p62: Intersection of Antioxidant Defense and Autophagy Pathways]. [p62]抗氧化防御和自噬途径的交叉[j]。
Molekulyarnaya Biologiya Pub Date : 2024-09-01 DOI: 10.31857/S0026898424050036, EDN: HURISK
G A Shilovsky
{"title":"[p62: Intersection of Antioxidant Defense and Autophagy Pathways].","authors":"G A Shilovsky","doi":"10.31857/S0026898424050036, EDN: HURISK","DOIUrl":"10.31857/S0026898424050036, EDN: HURISK","url":null,"abstract":"<p><p>Numerous regulatory cascades link the cell response to oxidative stress and the mechanisms that maintain homeostasis and cell viability. The review summarizes the molecular mechanisms of interaction of the autophagy protein p62 with cell defense systems, primarily through the NRF2/KEAP1/ARE pathway. Understanding the cross-regulation of antioxidant defense and autophagy pathways contributes to the search for promising molecular targets to prevent and treat age-related diseases.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 5","pages":"703-718"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Redox Status and Protein Glutathionylation in Binase-Treated HPV16-Positive SiHa Carcinoma Cells]. [binase处理hpv16阳性SiHa癌细胞的氧化还原状态和蛋白谷胱甘肽化]。
Molekulyarnaya Biologiya Pub Date : 2024-09-01 DOI: 10.31857/S0026898424050109, EDN: HUFEUW
A I Nadyrova, I Y Petrushanko, V A Mitkevich, O N Ilinskaya
{"title":"[Redox Status and Protein Glutathionylation in Binase-Treated HPV16-Positive SiHa Carcinoma Cells].","authors":"A I Nadyrova, I Y Petrushanko, V A Mitkevich, O N Ilinskaya","doi":"10.31857/S0026898424050109, EDN: HUFEUW","DOIUrl":"10.31857/S0026898424050109, EDN: HUFEUW","url":null,"abstract":"<p><p>Human papillomavirus type 16 (HPV16) belongs to viruses of the high-risk type and is associated by overexpression of E6 and E7 oncoproteins, which determine the oncogenic properties of the virus, such as immortalization and malignant transformation of proliferating epithelial cells. The biogenesis of redox-sensitive proteins E6 and E7 at the early stages of viral infection leads to blocking of the cell antioxidant defense system and ubiquintin-dependent degradation of p53 and Rb tumor suppressors. Maintaining high rates of tumor cell proliferation contributes to an increase in the level of reactive oxygen species (ROS) and a shift in the redox balance towards oxidative processes. Reduced glutathione (GSH) provides antioxidant protection to tumor cells through S-glutathionylation of thiol groups of redox-sensitive proteins, which leads to the appearance of multidrug-resistant forms of cancer. In this regard, drugs restoring redox balance and increasing susceptibility to antitumor therapy are of particular importance. We have established that, Bacillus pumilus RNase (binase) modulates the redox-dependent regulatory mechanisms that ensure tumor cell resistance to apoptosis in HPV-16-positive SiHa cells of cervical squamous cell carcinoma. Binase in nontoxic concentrations initiates a number of pre-apoptogenic changes, i.e., decreases ROS and reduced glutathione (GSH) levels, suppresses the expression of the E6 oncoprotein, activates the expression of the p53 tumor suppressor, and reduces the mitochondrial potential of tumor cells. Binase-induced disruption of the integrity of the mitochondrial membrane is a signal for activation of the mitochondrial apoptosis pathway.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 5","pages":"811-820"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Structure and Function of the Transglutaminase Cluster in the Basal Metazoan Halisarca dujardinii (Sponge)]. [基础后生动物Halisarca dujardinii(海绵)中转谷氨酰胺酶簇的结构和功能]。
Molekulyarnaya Biologiya Pub Date : 2024-09-01 DOI: 10.31857/S0026898424050094, EDN: HULTXR
A D Finoshin, O I Kravchuk, K V Mikhailov, R H Ziganshin, K I Adameyko, V S Mikhailov, Yu V Lyupina
{"title":"[Structure and Function of the Transglutaminase Cluster in the Basal Metazoan Halisarca dujardinii (Sponge)].","authors":"A D Finoshin, O I Kravchuk, K V Mikhailov, R H Ziganshin, K I Adameyko, V S Mikhailov, Yu V Lyupina","doi":"10.31857/S0026898424050094, EDN: HULTXR","DOIUrl":"10.31857/S0026898424050094, EDN: HULTXR","url":null,"abstract":"<p><p>Transglutaminases are enzymes that carry out post-translational modifications of proteins and participate in the regulation of their activities. Here, we show for the first time that the transglutaminase genes in the basal metazoan, the sea sponge Halisarca dujardinii, are organized in a cluster, similarly to mammalian transglutaminases. The regulatory regions of six transglutaminase genes and their differential expression in the course of the life cycle of H. dujardinii suggest independent regulation of these genes. The decrease in transglutaminase activities by cystamine facilitates restoration of the multicellular structures of this sponge after its mechanical dissociation. For the first time we observed that this decrease in transglutaminase activities was accompanied by generation of the reactive oxygen species in the cells of a basal metazoan. The study of transglutaminases in the basal metazoans and other sea-dwelling organisms might provide better understanding of the evolution and specific functions of these enzymes in higher animals.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 5","pages":"797-810"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[GRIP1 is Involved in the Interaction of Vimentin Filaments with Focal Adhesions in Endothelial Cells]. [GRIP1参与内皮细胞中静脉蛋白丝与局灶性粘连的相互作用]。
Molekulyarnaya Biologiya Pub Date : 2024-09-01 DOI: 10.31857/S0026898424050076, EDN: HUNTKB
F K Gyoeva
{"title":"[GRIP1 is Involved in the Interaction of Vimentin Filaments with Focal Adhesions in Endothelial Cells].","authors":"F K Gyoeva","doi":"10.31857/S0026898424050076, EDN: HUNTKB","DOIUrl":"10.31857/S0026898424050076, EDN: HUNTKB","url":null,"abstract":"<p><p>Vimentin intermediate filaments are dynamic structures that are able to move in cytoplasm owing to activity of the motor proteins, kinesin-1 and cytoplasmic dynein. How exactly motors interact with vimentin filaments remains unclear. In this work, I show that GRIP1 (Glutamate Receptor Interacting Protein 1), known as adapter for kinesin-1 on many cargoes in neurons, might also mediate kinesin-1 interaction with vimentin filaments. GRIP1 associates with vimentin filaments in various cells and co-immunoprecipitates with vimentin from cell lysates. Human endothelial cells knockout by GRIP1 gene lose focal adhesions and change their adhesive properties. Hypothetically, kinesin-1 engages GRIP1 to deliver vimentin filaments to the cell periphery so that they make contact with focal adhesions and stabilize them.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 5","pages":"772-783"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Expression of Long Noncoding RNAs and Protein-Coding Genes Involved in Oxidative Stress and Cell Senescence in Patients with Chronic Obstructive Pulmonary Disease]. [参与慢性阻塞性肺疾病患者氧化应激和细胞衰老的长链非编码rna和蛋白编码基因的表达]。
Molekulyarnaya Biologiya Pub Date : 2024-09-01 DOI: 10.31857/S0026898424050119, EDN: HUEBQI
V A Markelov, G F Korytina, Y G Aznabaeva, I A Gibadullin, L Z Akhmadishina, T R Nasibullin, O V Kochetova, A M Avzaletdinov, N Sh Zagidullin
{"title":"[Expression of Long Noncoding RNAs and Protein-Coding Genes Involved in Oxidative Stress and Cell Senescence in Patients with Chronic Obstructive Pulmonary Disease].","authors":"V A Markelov, G F Korytina, Y G Aznabaeva, I A Gibadullin, L Z Akhmadishina, T R Nasibullin, O V Kochetova, A M Avzaletdinov, N Sh Zagidullin","doi":"10.31857/S0026898424050119, EDN: HUEBQI","DOIUrl":"10.31857/S0026898424050119, EDN: HUEBQI","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a multifactorial heterogeneous chronic inflammatory respiratory disease. The molecular pathogenesis of COPD may include dysregulation of the stress responses that are associated with cell senescence and involve a wide range of signaling pathways and their epigenetic regulators, such as long noncoding RNAs (lncRNAs). To assess the contribution of genes involved in key signaling pathways related to cell senescence to the molecular pathogenesis of COPD, expression profiling of lncRNA (TP53TG1, LINC00342, H19, MALAT1, DNM3OS, and MEG3) and protein-coding (PTEN, TGFB2, FOXO3, and KEAP1) genes was performed in peripheral blood mononuclear cells of COPD patients (n = 92) and control subjects (n = 81). Significant downregulation of the TP53TG1 and DNM3OS lncRNAs and the TGFB2 mRNA was observed in the COPD patients, while the MALAT1 and LINC00342 were upregulated. A highly informative prognostic model was constructed based on the multiple regression and ROC analyses. The model included simultaneous assessment of the TP53TG1 and TGFB2 expression levels (AUC = 0.92). MALAT1, DNM3OS, TGFB2, FOXO3 and KEAP1 expression levels were found to positively correlate with lung function parameters, reflecting the disease progression. The lncRNA (TP53TG1, LINC00342, DNM3OS, and MALAT1) and protein-coding (TGFB2) genes that were differentially expressed in the COPD patients are functionally involved in regulating apoptosis, inflammation, fibrogenesis, and the epithelial-to-mesenchymal transition, implicating cell senescence processes in the molecular pathogenesis of COPD.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 5","pages":"821-839"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Metabolic Profile of Gut Microbiota and Levels of Trefoil Factors in Adults with Different Metabolic Phenotypes of Obesity]. [不同代谢表型肥胖成人肠道微生物群代谢特征和三叶因子水平]。
Molekulyarnaya Biologiya Pub Date : 2024-07-01 DOI: 10.31857/S0026898424040105, EDN: IMMUOM
I M Kolesnikova, L A Ganenko, I Yu Vasilyev, T V Grigoryeva, N I Volkova, S A Roumiantsev, A V Shestopalov
{"title":"[Metabolic Profile of Gut Microbiota and Levels of Trefoil Factors in Adults with Different Metabolic Phenotypes of Obesity].","authors":"I M Kolesnikova, L A Ganenko, I Yu Vasilyev, T V Grigoryeva, N I Volkova, S A Roumiantsev, A V Shestopalov","doi":"10.31857/S0026898424040105, EDN: IMMUOM","DOIUrl":"https://doi.org/10.31857/S0026898424040105, EDN: IMMUOM","url":null,"abstract":"<p><p>Obesity is associated with changes in the gut microbiota, as well as with increased permeability of the intestinal wall. In 130 non-obese volunteers, 57 patients with metabolically healthy obesity (MHO), and 76 patients with metabolically unhealthy obesity (MUHO), bacterial DNA was isolated from stool samples, and the 16S rRNA gene was sequenced. The metabolic profile of the microbiota predicted by PICRUSt2 (https://huttenhower.sph.harvard.edu/picrust/) was more altered in patients with MUHO than MHO. Obesity, especially MUHO, was accompanied by an increase in the ability of the gut microbiota to degrade energy substrates, produce energy through oxidative phosphorylation, synthesize water-soluble vitamins (B1, B6, B7), nucleotides, heme, aromatic amino acids, and protective structural components of cells. Such changes may be a consequence of the microbiota adaptation to the MUHO-specific conditions. Thus, a vicious circle is formed, when MUHO promotes the depletion of the gut microbiome, and further degeneration of the latter contributes to the pathogenesis of metabolic disorders. The concentration of the trefoil factor family (TFF) in the serum of the participants was also determined. In MHO and MUHO patients, the TFF2 and TFF3 levels were increased, but we did not find significant associations of these changes with the metabolic profile of the gut microbiota.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 4","pages":"638-654"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Human eRF1 Translation Regulation]. [人类eRF1翻译规则]。
Molekulyarnaya Biologiya Pub Date : 2024-07-01 DOI: 10.31857/S0026898424040091, EDN: IMNJKL
A V Shuvalov, A A Klishin, N S Biziaev, E Y Shuvalova, E Z Alkalaeva
{"title":"[Human eRF1 Translation Regulation].","authors":"A V Shuvalov, A A Klishin, N S Biziaev, E Y Shuvalova, E Z Alkalaeva","doi":"10.31857/S0026898424040091, EDN: IMNJKL","DOIUrl":"https://doi.org/10.31857/S0026898424040091, EDN: IMNJKL","url":null,"abstract":"<p><p>Eukaryotic translation release factor eRF1 is an important cellular protein that plays a key role in translation termination, nonsense-mediated mRNA decay (NMD), and readthrough of stop codons. The amount of eRF1 in the cell influences all these processes. The mechanism of regulation of eRF1 translation through an autoregulatory NMD-dependent expression circuit has been described for plants and fungi, but the mechanisms of regulation of human eRF1 translation have not yet been studied. Using reporter constructs, we studied the effect of eRF1 mRNA elements on its translation in cell-free translation systems and HEK293 cell culture. Our data indicate the absence of an NMD-dependent autoregulatory circuit for human eRF1 expression. We found that the translation of the eRF1 coding sequence is most strongly influenced by the 5' untranslated region of eRF1 mRNA and the start codon of the upstream open reading frame. According to the transcription start database, eRF1 mRNA is characterized by high heterogeneity of the transcription start and a variable 5' untranslated region in length. In addition, the start codon of the CDS in eRF1 mRNA is located within the known translational regulator of short 5' untranslated regions (TISU), which also stimulates mRNA transcription of genes with high transcription start heterogeneity. We hypothesize that regulation of human eRF1 synthesis occurs at both the transcriptional and translational levels. At the transcription level, the length of the eRF1 5' untranslated region and the number of the upstream open reading frames in it are regulated. This regulation in turn, regulates the production of eRF1 at the translation level.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 4","pages":"627-637"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Molecular Ion Channel Blockers of Influenza A and SARS-CoV-2 Viruses]. [甲型流感和SARS-CoV-2病毒的分子离子通道阻滞剂]。
Molekulyarnaya Biologiya Pub Date : 2024-07-01 DOI: 10.31857/S0026898424040125, EDN: IMBPHX
Yu N Vorobjev
{"title":"[Molecular Ion Channel Blockers of Influenza A and SARS-CoV-2 Viruses].","authors":"Yu N Vorobjev","doi":"10.31857/S0026898424040125, EDN: IMBPHX","DOIUrl":"https://doi.org/10.31857/S0026898424040125, EDN: IMBPHX","url":null,"abstract":"<p><p>Molecules were proposed to block the functional cycles of the influenza virus A and SARS-CoV- 2. The blocker molecules efficiently bind inside the M2 and E channels of influenza A and SARS-CoV-2 viruses and block diffusion of H^(+)/K^(+) ions, thus distorting the virus functional cycle. A family of positively charged (+2 e.u.) molecular blockers of H^(+)/K^(+) ion diffusion through the M2 and E channels was proposed. The blocker molecules were diazabicyclooctane (DABCO) derivatives and were investigated for affinity for the M2 and E channels. Thermal dynamics of native and mutant channel structures and blocker binding were modeled by exhaustive docking. Binding energy calculations revealed within-channel, blocking, and extrachannel binding sites in the M2 and E channel proteins. Blocker molecules with higher affinity for the blocking sites were proposed. The most probable amino acid mutations the M2 and E channels were considered, the efficiency of channel blocking was analyzed, and optimal structures were assumed for the blocker molecules.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 4","pages":"665-680"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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