Why the study?
Conserved yet dynamic structures in viral genome untranslated regions crucial for replication provide potential drug targets for broad-spectrum anti-virals.
Metallo-supramolecular cylinders can target specific RNA junctions in the SARS-CoV-2 genome and inhibit viral replication, suggesting potential as novel antiviral agents.
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May guide broad-spectrum antiviral design via viral UTR targeting; leaves open clinical translation pending validation.
The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with Molecular Dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5’ UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in the stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel antiviral agents.
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Melidis et al. (2021) studied this question.
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