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Host microRNAs exhibit differential propensity to interact with SARS-CoV-2 and variants of concern.
Capistrano, Kristelle J; Richner, Justin; Schwartz, Joel; Mukherjee, Sunil K; Shukla, Deepak; Naqvi, Afsar R.
  • Capistrano KJ; Mucosal Immunology Lab, College of Dentistry, University of Illinois Chicago, Chicago 60612, IL, USA.
  • Richner J; Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, Chicago 60612, IL, USA.
  • Schwartz J; Molecular Pathology Lab, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
  • Mukherjee SK; Division of Plant Pathology, Indian Agricultural Research Institute, New Delhi, India.
  • Shukla D; Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, Chicago 60612, IL, USA; Department of Ophthalmology and Visual Sciences, Ocular Virology Laboratory, University of Illinois Chicago, Chicago 60612, IL, USA.
  • Naqvi AR; Mucosal Immunology Lab, College of Dentistry, University of Illinois Chicago, Chicago 60612, IL, USA. Electronic address: afsarraz@uic.edu.
Biochim Biophys Acta Mol Basis Dis ; 1869(2): 166612, 2023 02.
Article in English | MEDLINE | ID: covidwho-2176723
ABSTRACT
A significant number of SARS-CoV-2-infected individuals naturally overcome viral infection, suggesting the existence of a potent endogenous antiviral mechanism. As an innate defense mechanism, microRNA (miRNA) pathways in mammals have evolved to restrict viruses, besides regulating endogenous mRNAs. In this study, we systematically examined the complete repertoire of human miRNAs for potential binding sites on SARS-CoV-2 Wuhan-Hu-1, Beta, Delta, and Omicron. Human miRNA and viral genome interaction were analyzed using RNAhybrid 2.2 with stringent parameters to identify highly bonafide miRNA targets. Using publicly available data, we filtered for miRNAs expressed in lung epithelial cells/tissue and oral keratinocytes, concentrating on the miRNAs that target SARS-CoV-2 S protein mRNAs. Our results show a significant loss of human miRNA and SARS-CoV-2 interactions in Omicron (130 miRNAs) compared to Wuhan-Hu-1 (271 miRNAs), Beta (279 miRNAs), and Delta (275 miRNAs). In particular, hsa-miR-3150b-3p and hsa-miR-4784 show binding affinity for S protein of Wuhan strain but not Beta, Delta, and Omicron. Loss of miRNA binding sites on N protein was also observed for Omicron. Through Ingenuity Pathway Analysis (IPA), we examined the experimentally validated and highly predicted functional role of these miRNAs. We found that hsa-miR-3150b-3p and hsa-miR-4784 have several experimentally validated or highly predicted target genes in the Toll-like receptor, IL-17, Th1, Th2, interferon, and coronavirus pathogenesis pathways. Focusing on the coronavirus pathogenesis pathway, we found that hsa-miR-3150b-3p and hsa-miR-4784 are highly predicted to target MAPK13. Exploring miRNAs to manipulate viral genome/gene expression can provide a promising strategy with successful outcomes by targeting specific VOCs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: MicroRNAs / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Biochim Biophys Acta Mol Basis Dis Year: 2023 Document Type: Article Affiliation country: J.bbadis.2022.166612

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Full text: Available Collection: International databases Database: MEDLINE Main subject: MicroRNAs / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Biochim Biophys Acta Mol Basis Dis Year: 2023 Document Type: Article Affiliation country: J.bbadis.2022.166612