Poster abstracts
Poster number 49 submitted by Caleb Frye
Host MicroRNA Interactions with the SARS-CoV-2 Viral Genome 3'-Untranslated Region
Caleb J. Frye (Department of Chemistry and Biochemistry, Duquesne University), Caylee L. Cunningham (Department of Chemistry and Biochemistry, Duquesne University), Mihaela Rita Mihailescu (Department of Chemistry and Biochemistry, Duquesne University)
Abstract:
The 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has marked the spread of a novel human coronavirus. SARS-CoV-2 has exhibited increased disease severity and immune evasion across its variants, and the molecular mechanisms behind these phenomena remain largely unknown. Conserved elements of the viral genome, such as secondary structures within the 3’-untranslated region (UTR), could prove crucial in furthering our understanding of the host-virus interface. Analysis of the SARS-CoV-2 viral genome 3’-UTR revealed the potential for host microRNA (miR) binding sites, allowing for sequence-specific interactions. In this study, we demonstrate that the SARS-CoV-2 genome 3’-UTR binds the host cellular miRNAs miR-760-3p, miR-34a-5p, and miR-34b-5p in vitro. Recent work has shown that these miRs influence translation of interleukin-6 (IL-6), the IL-6 receptor (IL-6R), and progranulin (PGRN), which are proteins key for the development of cytokine release syndrome (CRS), thus, highlighting potential implications in disease severity and immune evasion. Native gel electrophoresis and steady-state fluorescence spectroscopy were utilized to characterize the binding of these miRs to their predicted sites within the SARS-CoV-2 genome 3’-UTR. Additionally, we investigated 2’-fluoro-D-arabinonucleic acid (FANA) analogs of these miRNAs as competitive binding inhibitors for these miR binding interactions. The mechanisms detailed in this study have the potential to drive the development of antiviral treatments for SARS-CoV-2 infection and provide a potential molecular basis for CRS and immune evasion, which expands our breadth of knowledge of the host-virus interface.
Keywords: SARS-CoV-2, microRNAs, Hijacking