scholarly journals The miRNA Complexes Against Coronaviruses COVID-19, SARS-CoV, And MERS-CoV

2020 ◽  
Author(s):  
Aizhan Rakhmetullina ◽  
Anatoliy Ivashchenko ◽  
Aigul Akimniyazova ◽  
Dana Aisina ◽  
Anna Pyrkova
Keyword(s):  
Free Energy ◽  
Side Effects ◽  
Binding Sites ◽  
Untranslated Region ◽  
Messenger Rnas ◽  
High Concentration ◽  
Human Genes ◽  
Weak Binding ◽  
Simultaneous Inhibition ◽  
Interaction Free Energy

Abstract Background: In the past twenty years humankind has effected from infection caused by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and COVID-19 coronaviruses, which have caused significant harm to human health and resulted in high mortality. The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses COVID-19, SARS-CoV, and MERS-CoV has been shown. Methods: The MirTarget program determines the following characteristics of interaction between miRNAs and messenger RNAs (mRNAs): the start of the miRNA binding site on the mRNA; the locations of the miRNA binding sites in the 3'-untranslated region (3'UTR), 5'-untranslated region (5'UTR), or coding sequence (CDS); the interaction free energy (∆G, kJ/mole); and nucleotide interaction schemes between miRNAs and mRNAs. Results: Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of COVID-19, SARS-CoV, and MERS-CoV genomes. For complexes of seven completely complementary miRNA of COVID-19 (cc-miRc), seven completely complementary miRNA of SARS-CoV (cc-miRs), and eight completely complementary miRNA of MERS-CoV (cc-miRm), the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. Conclusion: The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

scholarly journals The miRNA COMPLEXES AGAINST CORONAVIRUSES SARS-CoV-2, SARS-CoV, and MERS-CoV

2020 ◽  
Author(s):  
Aizhan Rakhmetullina ◽  
Anatoliy Ivashchenko ◽  
Aigul Akimniyazova ◽  
Dana Aisina ◽  
Anna Pyrkova
Keyword(s):  
Free Energy ◽  
Side Effects ◽  
Binding Sites ◽  
Untranslated Region ◽  
Messenger Rnas ◽  
High Concentration ◽  
Human Genes ◽  
Weak Binding ◽  
Simultaneous Inhibition ◽  
Interaction Free Energy

Abstract Background: In the past twenty years humankind has effected from infections caused by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and SARS-CoV-2 coronaviruses, which have caused significant harm to human health and resulted in high mortality. The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses SARS-CoV-2, SARS-CoV, and MERS-CoV has been shown. Methods: The MirTarget program determines the following characteristics of interaction between miRNAs and messenger RNAs (mRNAs): the start of the miRNA binding site on the mRNA; the locations of the miRNA binding sites in the 3'-untranslated region (3'UTR), 5'-untranslated region (5'UTR), or coding sequence (CDS); the interaction free energy (∆G, kJ/mole); and nucleotide interaction schemes between miRNAs and mRNAs.Results: Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of SARS-CoV-2, SARS-CoV, and MERS-CoV genomes. For complexes of seven completely complementary miRNA of SARS-CoV-2 (cc-miRc), seven completely complementary miRNA of SARS-CoV (cc-miRs), and eight completely complementary miRNA of MERS-CoV (cc-miRm), the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. Conclusion: The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

scholarly journals The miRNA COMPLEXES AGAINST CORONAVIRUSES COVID-19, SARS-CoV, and MERS-CoV

2020 ◽  
Author(s):  
Anatoliy Ivashchenko ◽  
Aizhan Rakhmetullina ◽  
Aigul Akimniyazova ◽  
Dana Aisina ◽  
Anna Pyrkova
Keyword(s):  
Free Energy ◽  
Side Effects ◽  
Binding Sites ◽  
High Selectivity ◽  
High Concentration ◽  
Human Genes ◽  
Weak Binding ◽  
Simultaneous Inhibition

Abstract The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses COVID-19, SARS-CoV, and MERS-CoV has been shown. Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of COVID-19, SARS-CoV, and MERS-CoV genomes. For complexes of seven cc-miRc for COVID-19, seven cc-miRs for SARS-CoV, and eight cc-miRm for MERS-CoV, the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

scholarly journals Human Genes Are In Silico Potential Targets For Rice miRNA

2020 ◽  
Author(s):  
Aizhan Rakhmetullina ◽  
Anna Pyrkova ◽  
Dana Aisina ◽  
Anatoliy Ivashchenko
Keyword(s):  
Free Energy ◽  
Neurodegenerative Diseases ◽  
Candidate Genes ◽  
Human Body ◽  
Binding Sites ◽  
In Silico ◽  
Target Genes ◽  
A Value ◽  
Human Genes ◽  
Number Of Genes

AbstractExogenous miRNAs enter the human body through food, and their effects on metabolic processes can be considerable. It is important to determine which miRNAs from plants affect the expression of human genes and the extent of their influence. The binding sites of 738 osa-miRNAs that interact with 17508 mRNAs of human genes were determined using the MirTarget program. The characteristics of the binding of 46 single osa-miRNAs to 86 mRNAs of human genes with a value of free energy (ΔG) interaction equal 94% to 100% from maximum ΔG were established. The findings showed that osa-miR2102-5p, osa-miR5075-3p, osa-miR2097-5p, osa-miR2919 targeted the largest number of genes at 38, 36, 23, 19 sites, respectively. mRNAs of 86 human genes were identified as targets for 93 osa-miRNAs of all family osa-miRNAs with ΔG values equal 94% to 98% from maximum ΔG. Each miRNA of the osa-miR156-5p, osa-miR164-5p, osa-miR168-5p, osa-miR395-3p, osa-miR396-3p, osa-miR396-5p, osa-miR444-3p, osa-miR529-3p, osa-miR1846-3p, osa-miR2907-3p families had binding sites in mRNAs of several human target genes. The binding sites of osa-miRNAs in mRNAs of the target genes for each family of osa-miRNAs were conserved when compared to flanking nucleotide sequences. mRNA human genes of osa-miRNAs are candidate genes of cancer, cardiovascular and neurodegenerative diseases.

scholarly journals Specific Binding of Rubidium in Chlorella

1962 ◽  
Vol 45 (5) ◽  
pp. 959-977 ◽  
Author(s):  
Dan Cohen
Keyword(s):  
Active Transport ◽  
Binding Sites ◽  
Specific Binding ◽  
High Concentration ◽  
External Concentration ◽  
Specific Binding Sites ◽  
Dense Suspension ◽  
Concentration Of Ions ◽  
The Individual ◽  
A Site

Specific binding sites for potassium, which may be components of the carriers for active transport for K in Chlorella, were characterized by their capacity to bind rubidium. A dense suspension was allowed to take up Rb86 from a low concentration of Rb86 and a high concentration of ions which saturate non-specific sites. The amount bound was derived from the increase in the external concentration of Rb86 following addition of excess potassium. The sites were heterogeneous. The average affinity of Rb and various other ions for the sites was determined by plotting the degree of displacement of Rb86 against log molar concentration of the individual ions. Interpolation gave the concentration for 50 per cent displacement of Rb, which is inversely related to affinity. The order of affinity was not changed when the cells were frozen, or boiled either in water or in 70 per cent ethanol. The affinity is maximal for ions with a crystalline radius of 1.3 to 1.5 A and a high polarizability, and is not related to the hydrated radius or valency. It is suggested that binding groups in a site are rigidly arranged, the irregular space between them being 2.6 to 3.0 A across, so that affinity is high for ions of this diameter and high polarizability.

scholarly journals Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130018 ◽  
Author(s):  
Andrea I. Ramos ◽  
Scott Barolo
Keyword(s):  
Transcription Factor ◽  
Binding Affinity ◽  
Binding Sites ◽  
Target Genes ◽  
Gene Activation ◽  
Transcriptional Response ◽  
Morphogen Gradients ◽  
Weak Binding ◽  
Initial Hypothesis

In the era of functional genomics, the role of transcription factor (TF)–DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients . We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp , wingless and stripe , by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci-mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to-moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes.

Autoradiographic Localization of Opioid and Spirodecanone Receptors in the Gerbil Hippocampus as Compared with the Rat Hippocampus

1988 ◽  
Vol 8 (4) ◽  
pp. 568-574 ◽  
Author(s):  
Hiroshi Onodera ◽  
Kyuya Kogure
Keyword(s):  
Opioid Receptor ◽  
Binding Sites ◽  
Cellular Localization ◽  
Neuronal Damage ◽  
Pyramidal Cells ◽  
Rat Hippocampus ◽  
High Concentration ◽  
Receptor Sites ◽  
Ca3 Neurons

Opioid ([3H]naloxone) and spirodecanone ([3H]spiperone) binding sites in the hippocampus were visualized in the Mongolian gerbil and in the rat using in vitro autoradiography. In the hippocampus, marked differences were noted in the stratum (sr.) pyramidale of the CA1 subfield where opioid and spirodecanone (assayed in the presence of mianserin and sulpiride) binding activities were very low in gerbils, but high in rats. Gerbils exhibited a high concentration of [3H]naloxone binding sites in the sr. pyramidale of the CA3 subfield, as observed in the rat. In addition, the gerbil has a very high opioid receptor density in the hilar region and in the sr. moleculare of the dentate gyrus. The cellular localization of opioid and spirodecanone receptor sites was studied in the rat hippocampus using selective neuronal damage to CA1 and CA3 neurons by means of ischemia and kainic acid treatment, respectively. The results suggest that the gerbil differs from the rat with respect to the characteristic pyramidal cells (spirodecanone binding site) and interneurons (opioid receptor) in the CA1 subfield of the hippocampus. Distinct localization of opioid and spirodecanone receptors in the gerbil provides a good model with which to investigate the electrophysiological and biochemical roles of opioid peptides and butyrophenone spirodecanone drugs.

scholarly journals Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1217-1226 ◽  
Author(s):  
Yun Chen ◽  
David H. Gorski
Keyword(s):  
Binding Sites ◽  
Untranslated Region ◽  
Vascular Endothelial Cells ◽  
Homeobox Gene ◽  
Vascular Endothelial ◽  
Down Regulation ◽  
Antiangiogenic Activity ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Search

Abstract Angiogenesis is critical to tumor progression. The homeobox gene GAX inhibits angiogenesis in vascular endothelial cells (ECs). We have identified a microRNA (miR-130a) that regulates GAX expression and hypothesized that it plays a major role in modulating GAX activity in ECs. A 280-bp fragment from the GAX 3′-untranslated region (3′-UTR) containing 2 miR-130a targeting sites was observed to be required for the rapid down-regulation of GAX expression by serum and proangiogenic factors, whereas the activity of the GAX promoter did not vary with exposure to serum or proangiogenic factors. This same 280-bp sequence in the GAX 3′-UTR cloned into the psiCHECK2-Luciferase vector mediated serum-induced down-regulation of the reporter gene when placed 3′ of it. Finally, forced expression of miR-130a inhibits GAX expression through this specific GAX 3′-UTR sequence. A genome-wide search for other possible miR-130a binding sites revealed an miR-130a targeting site in the 3′-UTR of the antiangiogenic homeobox gene HOXA5, the expression and antiangiogenic activity of which are also inhibited by miR-130a. From these data, we conclude that miR-130a is a regulator of the angiogenic phenotype of vascular ECs largely through its ability to modulate the expression of GAX and HOXA5.

Genomics and Pharmacogenomics of Age-Related Hearing Loss

2021 ◽  
Vol 18 ◽  
Author(s):  
Joaquin Guerra ◽  
Vinogran Naidoo ◽  
Ramon Cacabelos
Keyword(s):  
Hearing Loss ◽  
Side Effects ◽  
Neurodegenerative Disorders ◽  
Therapeutic Targets ◽  
Vulnerable Population ◽  
Common Features ◽  
Control Side ◽  
Age Related ◽  
Human Genes ◽  
Age Related Hearing Loss

: Age-related hearing loss (ARHL) or presbycusis shares common features with conditions related to senescence and neurodegeneration. In this review, we explore the linking of genes involved in such processes with presbycusis, that has been proven to share important relationships with genes involved in dementia (APOE and MTHFR), ototoxicity (the GST group), and pharmacogenetics (NAT2). In this regard, we propose the construction of pharmacogenetics for the presbycusis database that could help better control side effects in this particularly vulnerable population susceptible to neurodegenerative disorders. Moreover, preliminary epigenetics studies have recently identified links in human genes involved in ARHL, which could serve as biomarkers or as therapeutic targets.

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