A prolonged pandemic with numerous human casualties requires a rapid search for means to control the various strains of SARS-CoV-2. Since only part of the human population is affected by coronaviruses, there are probably endogenous compounds preventing the spread of these viral pathogens. It has been shown that piRNA (PIWI-interacting RNAs) interact with the mRNA of human genes and can block protein synthesis at the stage of translation. Estimated the effects of piRNA on SARS-CoV-2 genomic RNA (gRNA) in silico. A cluster of 13 piRNA binding sites (BS) in the SARS-CoV-2 gRNA region encoding the oligopeptide was identified. The second cluster of BSs 39 piRNAs also encodes the oligopeptide. The third cluster of 24 piRNA BS encodes the oligopeptide. Twelve piRNAs were identified that strongly interact with the gRNA. Based on the identified functionally important endogenous piRNAs, synthetic piRNAs (spiRNAs) are proposed that will suppress the multiplication of the coronavirus even more strongly. These spiRNAs and selected endogenous piRNAs have little effect on human 17494 protein-coding genes, indicating a low probability of side effects. The piRNA and spiRNA selection methodology created for the control of SARS-CoV-2 (NC_045512.2) can be used to control all strains of SARS-CoV-2.
Viral diseases cause significant harm to human health and often cause high mortality. In the past twenty years, humanity has undergone infection by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and COVID-19 coronaviruses, which spread from animals to humans and from person to person. These diseases have led to large economic losses. To fight coronaviruses and other viruses, it is proposed to use miRNAs, which regulate protein synthesis at the translational level. MirTarget program was used to determine the following binding characteristics: the locations of miRNA binding sites in the 3'UTR, 5'UTR, and CDS; the free energy interaction ∆G between miRNA and mRNA; the ΔG/ΔGm value, where ΔGm is equal to the free energy binding of miRNA with its full complementary nucleotide sequence; and the nucleotide interaction schemes between miRNAs and mRNAs. Out of 2565 miRNAs, miR-4778-3p, miR-6864-5p and miR-5197-3p were identified as the most effectively interacting with the gRNA of SARS-CoV, MERS-CoV and COVID-19, respectively. Based on the miR-4778-3p, miR-6864-5p and miR-5197-3p sequences, complete complementary miRNA (cc-miR) binding sites in the gRNA coronaviruses were created. The detected binding sites of these cc-miRs did not form intramolecular complexes in the 2D structure of the gRNA of SARS-CoV, MERS-CoV, and COVID-19 with a value of more than 85%. Therefore, the cc-miRs will bind gRNA at these sites without competition. The cc-miRs for SARS-CoV, MERS-CoV, and COVID-19 did not have target genes among the 17508 human coding genes with a ΔG/ΔGm of more than 85%, which implies the absence of side effects of these cc-miRs on the translation of human mRNAs. cc-miRs can be used as therapeutic agents by incorporating them into exosomes or other vesicles and introducing them into the blood or lung by inhalation. The introduction of cc-miR into the blood will suppress the reproduction of the virus in the blood and in all organs into which it can enter. The proposed method of inhibiting the reproduction of coronaviruses can be used for other viruses.
Elucidation of ways to regulate the expression of candidate cancer genes will contribute to the development of methods for cancer diagnosis and therapy. The aim of the present study was to show the role of piRNAs as efficient regulators of mRNA translation of esophageal adenocarcinoma (EAC) candidate genes. We used bioinformatic methods to study the interaction characteristics of up to 200 thousand piRNAs with mRNAs of 38 candidate EAC genes. The piRNAs capable of binding to mRNA of AR, BTG3, CD55, ERBB3, FKBP5, FOXP1, LEP, SEPP1, SMAD4, and TP53 genes with high free energy by the formation of hydrogen bonds between canonical (G-C, A-U) and noncanonical (G-U, A-C) piRNA and mRNA nucleotide pairs were revealed. The organization of piRNA binding sites (BSs) in the mRNA of candidate genes was found to overlap nucleotide sequences to form clusters. Clusters of piRNA BSs were detected in the 5′-untranslated region, coding domain sequence, and 3′-untranslated region of mRNA. Due to the formation of piRNA binding site clusters, compaction of BSs occurs and competition between piRNAs for binding to mRNA of candidate EAC genes occurs. Associations of piRNA and candidate genes were selected for use as markers for the diagnosis of EAC.
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