Arginine-Rich Gold Silver–Nanoprobe for Rapid Virus Imaging and Real-Time Tracking in Infected Live-Cells

Virus imaging in infected live-cells is essential for clinical diagnostics and virology research. However, conventional nucleic acid probes suffer from low cellular internalization efficiency and poor intracellular stability and thus struggle to achieve efficient and sensitive virus imaging diagnostics. Here, histidine- and arginine-modified AuAg nanoclusters (CHR) are developed for rapid virus imaging and high-resolution real-time tracking in infected live-cells. Specifically, histidine can enhance the fluorescence intensity of AuAg nanoclusters through an electron-rich group. After conjugating DNA hairpin on CHR (CHR-h), it can maintain structural stability across pH 4.5–7.4 without false-positive signals. Arginine modification can accelerate rapid endocytosis through the guanidine-phosphate salt bridge with cell membrane, inducing CHR-h capture viral RNA within just 1 h via rapid cellular uptake and high fluorescence signal accumulation in living cells. Moreover, CHR-h reliably labels SARS-CoV-2’s genes with high infectivity through multitarget recognition to achieve real-time tracking of single viral particle. The dynamic separation of the single viral envelope and RNA is visualized and detailedly analyzed in the cytoplasm by total internal reflection fluorescence microscopy, providing insights into SARS-CoV-2’s infection mechanism in Vero E6 cells. Combining infected live-cell imaging and real-time tracking capabilities, CHR-h provides an efficient platform for virology research.