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

Noncoding RNA. 2021 Feb 18;7(1):14. doi: 10.3390/ncrna7010014. PMID: 33670580; PMCID: PMC7931055.

Authors/Editors: Natarelli L, Parca L, Mazza T, Weber C, Virgili F, Fratantonio D.
Publication Date: 2021

Abstract

The novel Coronavirus, SARS-CoV-2 disease (COVID-19) was defined as a global pandemic and induced a severe public health crisis in 2020. Covid-19 viral infection targets the human respiratory system and, at present, no specific treatment has been identified even though certain drugs have been studied and considered apparently effective in viral progression by reducing the complications in the lung epithelium. Researchers and clinicians are still struggling to find a vaccine or a specific innovative therapeutic strategy to counter COVID-19 infection.

Here we describe our study indicating that SARS-CoV-2 genome contains motif sequences in the 5´UTR leader sequence that can be selectively recognized by specific human non-coding RNAs (ncRNAs), such as micro and long non-coding RNAs (miRNAs and lncRNA). Notably, some of these ncRNAs have been already utilized as oligo-based drugs in pulmonary and virus-associated diseases. We identified three selective motifs at the 5´UTR leader sequence of SARS-CoV-2 that allow viral recognition and binding of a specific group of miRNAs, some of them characterized by “GU” seed alignments. Additionally, one seed motif within miRNAs has been found to be able to bind the 5’UTR leader sequence. Among miRNAs having thermodynamically stable binding site against leader sequence and that are able interacted with Spike transcript some are involved in pulmonary arterial hypertension and anti-viral response, i.e. miR-204, miR-3661, and miR-1343. Moreover, several miRNA candidates have been already validated in vivo and specific oligo sequence are indeed available for their inhibition or overexpression.

Four lncRNAs (H19, Hotair, Fendrr, and LINC05) directly interact with spike transcript (mRNA) and viral genome.

In conclusion, we suggest that specific miRNAs and lncRNAs can be potential candidates to design oligonucleotide-drugs to treat COVID-19 and that our study can provide candidate hypothesis to be eventually tested in further experimental studies.

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