In Situ Noninvasive Observation of Nitric Oxide Fluctuation in SARS-CoV-2 Infection In Vivo by Organic Near-Infrared-II Fluorescent Molecular Nanoprobes

The pathogenesis understanding of SARS-CoV-2 infection is crucial to prevent the rampant spread of COVID-19 and its contribution to deterioration in health, even death. Nitric oxide (NO), a crucial molecule involved in signal transduction and cytotoxicity, is a possible key regulator in the occurrence and development of COVID-19. However, understanding the pathogenesis of NO in SARS-CoV-2 infection is still in its infancy due to the lack of suitable in situ monitoring probes of NO fluctuation in the complex SARS-CoV-2 infection environment in deep lung tissues. Herein, we developed an activatable near-infrared-II fluorescent molecular nanoprobe (OSNP) that uncages high-resolution and deep-tissue-penetrating near-infrared-II fluorescence signal in specific response to NO for in situ and noninvasive visualization of NO fluctuation in a SARS-CoV-2 infection mouse model in lung tissues. In vivo visualization revealed that the NO level is a positive relationship with SARS-CoV-2 infection progress. With the assistance of immuno-histochemical analyses, we uncovered the NO-involved pathological mechanism, that being the improved NO level is associated with an increase in inducible NO synthase rather than endothelial NO synthase. Our study not only provides the example of a near-infrared-II fluorescent imaging of NO in SARS-CoV-2 infection but also provides opportunities to uncover tunderlying pathomechanism of NO for SARS-Cov-2 infections.