MicroRNAs and Long Non-Coding RNAs as Potential Candidates to Target Specific Motifs of SARS-CoV-2

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• The respiratory system is significantly impacted by SARS-CoV-2, necessitating novel therapeutic strategies beyond vaccines.
• Existing therapies for viral-induced inflammation show varied efficacy, highlighting the need for new approaches.
• Targeting viral genetic material offers a promising avenue for developing specific antiviral therapies.

Purpose of the Study:

• To computationally investigate potential binding sites within the SARS-CoV-2 genome for endogenous human microRNAs (miRNAs) and long non-coding RNAs (lncRNAs).
• To establish a conceptual framework for developing miRNA-based therapeutics against COVID-19.
• To identify specific non-coding RNAs capable of inhibiting SARS-CoV-2 gene expression.

Main Methods:

• Computational analysis of the SARS-CoV-2 genome, focusing on the 5' untranslated region (5'UTR).
• Identification of target motifs within the viral genome suitable for binding with human miRNAs and lncRNAs.
• Assessment of non-canonical binding mechanisms, including offset-6mer sites and "GGG" motifs.

Main Results:

• Three motifs were identified in the SARS-CoV-2 5'UTR leader sequence capable of binding specific human miRNAs.
• A "GGG" motif in 57 miRNAs facilitated non-canonical binding to the viral RNA via offset-6mer sites.
• Long non-coding RNA H19 demonstrated binding to the viral 5'UTR and the Spike gene transcript.

Conclusions:

• Endogenous human miRNAs and lncRNAs represent potential therapeutic agents against SARS-CoV-2 by targeting its genome.
• The identified binding interactions provide a foundation for developing novel miRNA-based drugs for COVID-19 treatment.
• Some candidate non-coding RNAs have prior associations with inhibiting other viral infections and related diseases.