A new study reveals that a simple taste could one day tell you if you have the flu, thanks to a chemically engineered sensor that uses your tongue as a built-in diagnostic tool.
Study: A Viral Neuraminidase-Specific Sensor for Taste-Based Detection of Influenza. Image Credit: Corona Borealis Studio / Shutterstock.com
A recent study published in ACS Central Science examines the effectiveness of a novel taste-based sensor for the early detection of influenza infection.
Historical influenza outbreaks
Influenza is a viral infection that causes acute respiratory disease and is responsible for approximately 500,000 deaths every year. Common influenza-causing virus subtypes include influenza A H1N1 and H3N2, as well as influenza B lineages like Victoria and Yamagata. Influenza subtypes, which are primarily responsible for seasonal flu outbreaks in humans, can be further categorized based on the presence of surface enzymes neuraminidase and hemagglutinin.
Influenza infections have significantly decreased since 2020 due to personal protective measures adopted during the coronavirus disease 2019 (COVID-19) pandemic to prevent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission. Despite this decline, seasonal influenza continues to circulate worldwide to cause severe illness, hospitalization, and death, particularly among vulnerable populations.
Between 1918 and 1920, the Spanish flu, which was followed by several H1N1 viral waves, affected over 25% of the global population. During the H1N1 epidemic in 2009, most deaths were reported in people 65 years and younger, which was a unique pattern as compared to previous influenza outbreaks.
Influenza viruses are transmitted through both animals and birds. Between 2022 and 2024, zoonoses were reported from poultry, dairy cows, and unknown animal sources in the United Kingdom, with H5N1 identified as the dominant variant.
How is influenza diagnosed?
In many countries throughout the world, federal resources are widely allocated to advance influenza diagnostics, treatments, and vaccines. Within the United States, the National Strategy for Pandemic Influenza Implementation Plan is primarily focused on the development of diagnostic devices to distinguish between people infected with the influenza virus and those who are healthy.
The polymerase chain reaction (PCR) assay is an extremely sensitive and specific method that is typically used to diagnose influenza infection. Despite its utility, this assay is time-consuming and its widespread application is logistically challenging, particularly for low-income countries, due to its high cost.
Most serological influenza tests will produce inaccurate results for individuals with asymptomatic infections. Thus, there is an urgent need for improved diagnostics capable of detecting influenza infection, particularly among presymptomatic yet contagious patients.
About the study
The researchers of the current study designed two novel sensors and evaluated their efficacy in detecting the early phases of influenza infection through taste. Whereas the unmethylated reference sensor was designed by linking thymol (O-glycosidically) to unmodified N-acetylneuraminic acid (Neu5Ac), thymol was O-glycosidically linked to 4,7-di-O-methyl-N-acetylneuraminic acid in the other sensor.
Within these sensors, thymol is in a protected state that prevents its release unless exposed to the viral neuraminidase, which leads to cleavage of the glycosidic bond that the user perceives as a taste signal. To ensure diagnostic accuracy, both sensors were tested against H1N1 neuraminidase and bacterial neuraminidase isolated from Micromonospora viridifaciens.
Study findings
To clinically define neuraminidase levels, saliva samples were collected from hospitalized, PCR-positive influenza patients during both the 2017/2018 and 2022/2023 influenza seasons. Neuraminidase activity did not differ significantly between the seasons.
Neuraminidase levels within the range of 5-10 mU/mL were estimated in sensor analyses. The results of commercially available assays based on the unmethylated neuraminic acid backbone at positions O4 and O7 were similar to those of the unmethylated reference sensor.
The recombinant influenza neuraminidase efficiently cleaved the unmethylated sensor when thymol was released, thus reflecting its specificity. These findings demonstrate that α-glycosidic coupling of the reporter moiety is essential for both enzymatic recognition and signal generation.
Chemical modification of the N-acetylneuraminic acid scaffold enabled selective cleaving by the viral neuraminidase without reacting to the bacterial form of this enzyme. These observations persisted, even at enzyme concentrations equivalent to those detected in the saliva of influenza-positive patients.
The study further demonstrated that the modified (methylated) α-sensor responded selectively to viral neuraminidase within 30 minutes, while remaining stable in the presence of bacterial neuraminidase and in unspiked human saliva.
We designed and chemically optimized neuraminidase-responsive molecules that release a tasteable reporter when cleaved and demonstrated that these sensors can detect viral enzyme activity in patient saliva at physiologically relevant levels.”
While the study showed enzyme-specific detection in saliva samples, it did not include in vivo testing to confirm that individuals could perceive the taste signal themselves. The authors emphasize that future studies must validate this sensory detection in clinical settings.
Conclusions
The researchers developed a novel taste-based sensor to detect influenza infection at an early stage, which has the potential to distinguish between healthy individuals and those who are asymptomatic but recently infected. However, the current findings are based on biochemical and saliva-sample analyses rather than direct human testing.
Despite these observations, additional clinical studies are needed to validate the sensitivity of this sensor before its clinical use. If validated, the approach could provide an accessible, low-cost screening method for rapid first-line influenza detection.
Journal reference:
- Raschig, M., Gutmann, M., Kehrein, J., et al. (2025) A Viral Neuraminidase-Specific Sensor for Taste-Based Detection of Influenza. ACS Central Science. doi:10.1021/acscentsci.5c01179