Recently, the team led by Su Xin and Tong Yigang from the School of Life Sciences and Technology published a research paper entitled Direct visualization of RNA virus and evaluation of drug effect in living cells by catalytically transformable DNA cube in the internationally renowned journal Science Advances. This research developed a catalytically transformable DNA cube (CAT-Cube) that combines viral RNA recognition, signal amplification, and high-brightness fluorescence output into a compact DNA nanostructure, enabling direct visualization of RNA viruses within living cells and further applying it to the evaluation of the efficacy and mechanism of antiviral drugs.
Traditional virus detection methods, such as RT-PCR, immunofluorescence, and plaque assays, typically rely on nucleic acid extraction, cell fixation, or endpoint detection, making it difficult to reflect the real-time viral infection and drug response processes within living cells. To address this issue, the research team assembled a catalytic hairpin confinement system within a rigid DNA cube. Leveraging its autonomous cellular entry, enhanced local reaction concentration, viral RNA recycling, and high-brightness, stable signal output, this system enables dynamic imaging of intracellular viral RNA. This system can detect SARS-CoV-2 virus-like particles (trVLPs) with transcriptional and replication capabilities down to an MOI of 0.1, and allows direct observation of the effects of antiviral molecules such as ACE2 inhibitors, nucleic acid aptamers, and the natural product Cepharanthine. Further combining molecular dynamics simulations and transcriptome analysis, the study revealed a dual-target antiviral mechanism of Cepharanthine, acting simultaneously on the host ACE2 receptor and the viral spike protein. This work provides a novel programmable nanotool for dynamic studies of RNA viruses in living cells and for in-situ evaluation of antiviral drugs.
Schematic diagram of CAT-Cube for detecting RNA viruses
Paper link: https://www.science.org/doi/10.1126/sciadv.aee2515