How miRNAs can protect humans from coronaviruses COVID-19, SARS-CoV, and MERS-CoV

Ivashchenko At, Aizhan Rakhmetullina, Dana Aisina

2020

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.21203/rs.3.rs-16264/v1
Data confidence 70 medium
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Abstract

Abstract 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.