Identification of Human miRNA Biomarkers Targeting the SARS-CoV-2 Genome.

ABSTRACT

SARS-CoV-2 poses a great challenge toward mankind, majorly due to its evolution and frequently occurring variants. On the other hand, in human hosts, microRNA (miRNA) plays a vital role in replication and propagation during a viral infection and can control the biological processes. This may be essential for the progression of viral infection. Moreover, human miRNAs can play a therapeutic role in treatment of different viral diseases by binding to the target sites of the virus genome, thereby hindering the essential functioning of the virus. Motivated by this fact, we have hypothesized a new approach in order to identify human miRNAs that can target the mRNA (genome) of SARS-CoV-2 to degrade their protein synthesis. In this regard, the multiple sequence alignment technique Clustal Omega is used to align a complement of 2656 human miRNAs with the SARS-CoV-2 reference genome (mRNA). Thereafter, ranking of these aligned human miRNAs is performed with the help of a new scoring function that takes into account the (a) total number of nucleotide matches between the human miRNA and the SARS-CoV-2 genome, (b) number of consecutive nucleotide matches between the human miRNA and the SARS-CoV-2 genome, (c) number of nucleotide mismatches between the human miRNA and the SARS-CoV-2 genome, and (d) the difference in length before and after alignment of the human miRNA. As a result, from the 2656 ranked miRNAs, the top 20 human miRNAs are reported, which are targeting different coding and non-coding regions of the SARS-CoV-2 genome. Moreover, molecular docking of such human miRNAs with virus mRNA is performed to verify the efficacy of the interactions. Furthermore, 4 miRNAs out of the top 20 miRNAs are identified to have the seed region. In order to inhibit the virus, the key human targets of the seed regions may be targeted. Repurposable drugs like carfilzomib, bortezomib, hydralazine, and paclitaxel are identified for such purpose.