Mircovid-19: Potential targets of human mirnas in sars-cov-2 for rna-based drug discovery

Tanvir Alam*, Leonard Lipovich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Sense-antisense interactions of long and short RNAs in human cells are integral to post-transcriptional gene regulation, in particular that of mRNAs by microRNAs. Many viruses, including severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 (the causative agent of coronavirus disease 2019, COVID-19), have RNA genomes, and interactions between host and viral RNAs, while known to be functional in other viral diseases, have not yet been investigated in COVID-19. To remedy this gap in knowledge, we present miRCOVID-19, a computational meta-analysis framework identifying the predicted binding sites of human microRNAs along the SARS-CoV-2 RNA genome. To highlight the potential relevance of SARS-CoV-2-genome-complementary miRNAs to COVID-19 pathogenesis, we assessed their expression in COVID-19-relevant tissues using public transcriptome data. miRCOVID-19 identified 14 high-confidence mature miRNAs that are highly likely to interact with the SARS-CoV-2 genome and are expressed in diverse respiratory epithelial and immune cell types that are relevant to COVID-19 pathogenesis. As a proof of principle, we have shown that human miR-122, a previously known co-factor of another RNA virus, the hepatitis C virus (HCV) whose genome it binds as a prerequisite for pathogenesis, was predicted to also bind the SARS-CoV-2 RNA genome with high affinity, suggesting the perspective of repurposing anti-HCV RNA-based drugs, such as Miravirsen, to treat COVID-19. Our study is the first to identify all high-confidence binding sites of human miRNAs in the SARS-CoV-2 genome using multiple tools. Our work directly facilitates experimental validation of the reported targets, which would accelerate RNA-based drug discovery for COVID-19 and has the potential to provide new avenues for treating symptomatic COVID-19, and block SARS-CoV-2 replication, in humans.

Original languageEnglish
Article number18
JournalNon-coding RNA
Volume7
Issue number1
DOIs
Publication statusPublished - 2021

Keywords

  • Antagomir
  • Anti-miR
  • COVID-19
  • Coronavirus
  • HCV
  • MiR-122
  • MiRNA
  • MicroRNA
  • Miravirsen
  • RNA therapeutics
  • SARS-CoV-2

Fingerprint

Dive into the research topics of 'Mircovid-19: Potential targets of human mirnas in sars-cov-2 for rna-based drug discovery'. Together they form a unique fingerprint.

Cite this