ArticleComputational and structural biotechnology journal2026
Functional Genomic Evidence for Candidate Small Viral RNA-Mediated Epigenetic Interference in SARS-CoV-1 and SARS-CoV-2.
Article in Computational and structural biotechnology journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
3 authors.
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Abstract
Small viral RNAs (svRNAs) have emerged as key factors in host adaptation and virulence, with evidence of their presence in both SARS-CoV-2 and SARS-CoV-1. Here, using functional genomics, we identify 6 candidate svRNA-triplex-forming oligonucleotides (svRNA-TFOs) in SARS-CoV-2 and, through comparative analyses with SARS-CoV-1, delineate evolutionary pathways for svRNA-TFOs in Sarbecoviruses. In addition to the significant enrichment of candidate svRNA-TFO enhancer-gene targets among differentially expressed genes during SARS-CoV-2 infection, these svRNA-TFOs also show nonrandom associations with over 25% of the recombination breakpoints and hotspots in the Wuhan-Hu-1 genome. Small RNA-sequencing reveals highly abundant svRNA-TFO-N derived from the nucleocapsid of SARS-CoV-2. Using synonymous-site conservation analysis, we show that svRNA-TFO-N and other svRNA-TFOs are conserved among both SARS-CoV-2- and SARS-CoV-1-related lineages. Furthermore, BLASTn reveals that svRNA-TFO-N and svRNA-TFO-S.1 share sequence homology against various mammalian genomes, which supports a proposed mechanism of host adaptation. Finally, based on RNA structural modeling, we identify variant of concern-associated S:D614G and N:D377Y mutations, which may alter precursor structures predicted for svRNA-TFO-S.1 and svRNA-TFO-N, respectively. Collectively, these findings provide support for the hypothesis that svRNA-mediated epigenetic interference contributes to virulence in SARS-CoV-2 and SARS-CoV-1.
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Registered trials
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