A Viral Neuraminidase-Specific Sensor for Taste-Based Detection of Influenza

Influenza has caused the deadliest pandemics in history, thereby prompting advances in our ability to ensure vigilance at all stages of future outbreaks. Quarantining patients early is crucial when it comes to preventing these outbreaks, but it is challenging with influenza due to presymptomatic transmission. Presymptomatic detection translates into massive screening needs, which necessitate cost-effective tools with access for anyone, anywhere, and at any time. We met these challenges by synthesizing sensors that respond to influenza infections with taste generation by using the tongue as an always-available detector. In doing so, we utilized the virus's need for neuraminidase cleavage of α-glycosidic bonds to detect its presence in patients. We synthesized <i>N</i>-acetylneuraminic acid-thymol derivatives and chemically tuned them to respond to viral but not bacterial neuraminidase. Viral selectivity was further confirmed via structural analysis and molecular docking. Influenza sensors that respond to viral presence with taste may have unmatched advantages regarding accessibility and cost-effectiveness, including the potential to first-line stratify millions of healthy individuals from flu patients, thereby enabling us to leverage our response armamentarium in future outbreaks.