Selective activity of american cranberry juice exhibits against SARS-CoV-2 Mpro in a phenotypic bacterial assay

BACKGROUND: Breakthroughs SARS-CoV-2 main protease (Mpro) remains a central antiviral target due to its essential role in viral replication and high conservation among coronaviruses. Early-stage prioritization of candidate inhibitors, particularly from complex natural matrices, requires functional systems that are experimentally accessible, biosafe, and compatible with crude preparations. We previously developed a bacterial colorimetric reporter assay that couples intracellular Mpro activity to β-galactosidase output in a genetically engineered Escherichia coli strain. AIM: The present study aimed to evaluate juice preparations derived from four closely-related and widely consumed Vaccinium species: northern highbush blueberry (Vaccinium corymbosum L.), lingonberry (Vaccinium vitis-idaea L.), swamp cranberry (Vaccinium oxycoccos L.), and American cranberry (Vaccinium macrocarpon Ait.) for the potential to produce a functional inhibitory signal against Mpro using our previously established assay. METHODS: The evaluation was performed using our previously developed bacterial colorimetric reporter assay that couples intracellular Mpro activity to β-galactosidase output in E. coli. RESULTS: Under identical experimental conditions, northern highbush blueberry, lingonberry, and swamp cranberry juices did not restore reporter signal at any tested concentration. In contrast, American cranberry juice produced a detectable gain-of-signal response at two lower concentrations, whereas higher concentrations resulted in reporter-specific interference confirmed by internal controls. This pattern suggests the presence of bioactive compounds in cranberry juice that may modulate galactosidase-associated readout at higher concentrations. CONCLUSION: Such observations are relevant for future studies aimed at identifying anti-COVID drug candidates and evaluating potential biological effects associated with complex plant-derived preparations. Collectively, these findings prioritize American cranberry as a candidate for further evaluation within defined experimental boundaries.