Influenza is one of the most significant respiratory infections, which kills approximately 500,000 people every year. The virus includes types A and B, with A further classified according to hemagglutinin (H) and neuraminidase (N) subtypes. The number of cases decreased in 2020 and 2021 due to measures against COVID-19, but the threat of a global outbreak remains high. There have been previous pandemics, including the 1918 Spanish flu and the H1N1 outbreak in 2009, that were highly fatal. Recent zoonotic infections, such as the H5N1 outbreak in animals in the U.S. (2022 & 2024), are a reminder of the current threat and the necessity of robust pandemic preparedness. Â
Large-scale and quick testing is crucial to be ready for future outbreaks of flu. PCR tests are reliable yet costly and time-consuming, whereas serological tests are not reliable in the early stages of infection, which underscores the necessity of having a low-cost, rapid diagnostic tool.
Researchers have developed a taste-based technique that utilizes human saliva to identify viral neuraminidase, an enzyme that breaks α-glycosidic bonds during viral replication. They synthesized an N-acetylneuraminic acid conjugated to thymol that produces a different taste when digested by neuraminidase. Such sensors may be incorporated into chewing gum, dissolvable films, or a portable device in the future to do quick self-testing.
Two sensors were developed, one of which, sensor 15, is a 4,7-di-O-methyl derivative that has greater viral neuraminidase selectivity. It was found to be 94% stable at 50 °C after 4 weeks, was not cytotoxic, and retained greater than 90% cell viability at 1.0 mM. Â
 Neuraminidase activity was determined in the saliva of influenza-positive patients during the 2017-2018 and 2022-2023 seasons and was 8.9 ± 6.5 mU/mL and 13.4 ± 8.3 mU/mL, respectively, with no differences between seasons. The Sensor 15 was used to identify viral neuraminidase in 30 minutes, and the sensor used was the unmodified sensor, as it responded to viral and bacterial enzymes. Live H1N1 tests were found to release thymol at 0.013-0.028 mM, and 0.11- 0.27 mM (like patient saliva). The sensor required to achieve the taste threshold is approximately 2.1-11.5mg. Replacement of thymol by denatonium may enhance sensitivity by 100 times. Â
The structural modeling confirmed that methylation of the sugar molecule in O4 and O7 positions inhibits bacteriophages but does not inhibit the viral enzyme attachment. This selectivity resulted from docking simulations. In conclusion, the present taste-activated sensor is an excellent platform that provides quick, cheap, and distributable saliva-based influenza detection. It is a viral neuraminidase selective and may be used in simple consumer formats like chewing gum, which may make it a useful device in early screening and pandemic preparedness on a global scale.Â
Reference:Â Raschig M, Gutmann M, Kehrein J, et al. A viral neuraminidase-specific sensor for taste-based detection of influenza. ACS Cent Sci. 2025; doi:10.1021/acscentsci.5c01179Â
