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

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Abstract

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.

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About the authors

Shaza S. Issa

Saint Petersburg State University

Email: Shaza.Issa98@outlook.com
ORCID iD: 0000-0002-1690-0199
SPIN-code: 9610-5674
Russian Federation, Saint Petersburg

Tatiana V. Matveeva

Saint Petersburg State University; All-Russian Institute of Plant Protection

Author for correspondence.
Email: radishlet@gmail.com
ORCID iD: 0000-0001-8569-6665
SPIN-code: 3877-6598

Dr. Sci. (Biology), Professor

Russian Federation, Saint Petersburg; Saint Petersburg

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2. Fig. 1. Biological activity of American cranberry juice against E. coli expressing the Mpro protein of SARS-CoV-2: a, absorbance values at 650 nm for E. coli cultures incubated with V. macrocarpon juice. Bars represent mean absorbance ± SD (n = 3). Absorbance values were normalized to juice-only, no-X-gal controls; b, OD600 measurements for cultures incubated with cranberry juice. Initial OD600 was standardized across all cultures. Differences between groups were first evaluated using the Kruskal–Wallis test, followed by Dunn’s multiple comparison test with adjustment for multiple comparisons. Asterisks indicate statistically significant differences compared to untreated controls (p < 0.05).

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