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Fruits of  Citrus sinensis  L. Osbeck var. Valencia contain hesperidin as a major flavanone glycoside. Hesperidin (H) was isolated from the peels of Valencia orange and formulated as hexosomal nanodispersions (F1) adopting the hot emulsification method. The antimycobacterial activity(anti-TB) was evaluated through a microplate Alamar blue (MABA) assay where F1 showed significant activity with MIC = 0.19 µM. To unravel the potential mechanism of the anti-TB, a molecular docking study of H using the Mycobacterial Dihydrofolate reductase (Mtb. DHFR) enzyme was performed. Hesperidin exhibited significant interactions with Mtb. DHFR active site. Sulforhodamine B assay was applied to evaluate cytotoxic activity against the lung cancer cell line (A-549). F1 showed a cytotoxic effect at IC 50 = 33 µM. It also has potent antiviral activity against Human Coronavirus 229E with IC 50 = 258.8 μM utilising crystal violet assay. Peels of Valencia orange could be a source of bioactive metabolites to control significant diseases.

Hesperidin hexosomal loaded nanodispersion: insights of its antimycobacterial, cytotoxic and anti-HCoV effects