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

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.

The Role of miRNAs in COVID-19 Disease

“…For instance, ID02510.3p-miRNA, ID00448.3pmiRNA, miRNA 3154, miRNA 7114-5p, miRNA 5197-3p, ID02750.3p-miRNA and ID01851.5p-miRNA, miR-5197-3p [ 12 , 13 ], miR-17-5p and miR-20b-5p [ 14 ] mitigate the pathogenesis of COVID-19 disease via binding to the SARS-CoV-2 genome and inhibit its post-transcriptional expression. Nersisyan et al introduced six miRNAs including miR-21-3p, miR-195-5p, miR-16-5p, miR-3065-5p, miR-424-5p and miR-421 that potentially regulated all human coronaviruses through direct binding to the viral genome.…”

SARS-CoV-2 and miRNA-like inhibition power

“…To conclude, the natural history of the SARS-CoV-2 virus remains widely unknown and it is still too early to say whether the many mutations observed will cause it to evolve in a favorable direction from a human point of view. There are for example some mutations surely deleterious [71] , [72] , but also others favoring the positive role of some human miRNAs against SARS-CoV-2 [73] , [74] , [75] suggesting a possible therapy. The present proposal of a miRNA-like mechanism would at least allow to see, for a predictive purpose, what mutations (depending for example on geoclimatic factors [76] ) are keeping, losing or reinforcing its pathogenicity.…”

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].…”