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

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.

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities

“…The proposed miR1307 has been suggested as a therapeutic target in the prevention of SARS-CoV-2 infection. Therefore, more studies on in silico patterns within the SARS-CoV-2 genome may provide a deeper understanding about miR-based novel therapeutics [117,118]. MERS shows greater divergence across these segments and the two milder symptom viruses show even greater differences or even significant sequence gaps.…”

COVID-19: fighting the invisible enemy with microRNAs

“…Another method to control COVID-19 and/or other two coronavirus diseases is, to utilize completely complementary miRNAs (cc miRNA) that can target the viral gene and inhibit its posttranscriptional expression. The cc miRNAs (modified to 25-27 nucleotides), namely, ID02510.3p-miRNA, ID00448.3p-miRNA, miRNA 3154, miRNA 7114-5p, miRNA 5197-3p, ID02750.3p-miRNA, and ID01851.5p-miRNA showed a strong binding with the SARS-CoV-2 viral genome, suggestively [58].…”

Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting

“…An interaction between human coronavirus OC43 nucleocapsid and miR-9 can enhance the type I interferon response necessary to clear viral infection [ 21 ]. Several host miRNAs (miR-574-5p, −214, −17, −98, −223, and −148a) bind to SARS-CoV encoded transcripts such as S, E, M, N, and ORF1a [ 22 , 23 ]. However, SARS-CoV escapes from miRNA-mediated defence through the manipulation of host miRNA machinery [ 22 , 23 ].…”

“…Several host miRNAs (miR-574-5p, −214, −17, −98, −223, and −148a) bind to SARS-CoV encoded transcripts such as S, E, M, N, and ORF1a [ 22 , 23 ]. However, SARS-CoV escapes from miRNA-mediated defence through the manipulation of host miRNA machinery [ 22 , 23 ]. Additionally, SARS-CoV and SARS-CoV-2 express short RNAs that resemble miRNAs and could impact upon host house-keeping or immune defence processes [ 24 , 25 , 26 ].…”