Hesperidin identified from Citrus extracts potently inhibits HCV genotype 3a NS3 protease

• DOI: 10.1186/s12906-022-03578-1
• Publication Date: 2022-04-02T11:03:24Z
• Authors: Mahim Khan; Waqar Rauf; Fazal-e- Habib; Moazur Rahman; Shoaib Iqbal; Aamir Shehzad; Mazhar Iqbal
• Keywords: NS3; Tobacco etch virus; Darunavir

Hepatitis C virus infection is the main cause of liver ailments across globe. Several HCV genotypes have been identified in different parts world. Effective drugs for combating infections are available but not affordable, particularly to infected individuals from resource-limited countries. Hence, cost-effective need be developed against important drug targets. As Citrus fruits naturally contain bioactive compounds with antiviral activities, current study was designed identify inhibitors fruit extracts an target, NS3 protease, genotype 3a which found predominantly South Asian countries.The full-length protease alone and domain fusion cognate NS4A cofactor were expressed Escherichia coli, purified by chromatographic techniques. Using protein as a evaluated FRET assay, active ingredients, using ESI-MS/MS, docked observe interaction site residues NS3. The best interacting compound further confirmed through assay inhibitor protease.Fusion significantly improved purification yield, NS3-NS4A functionally more than alone. (NS3-NS4A) successfully employed validated evaluate 14 extracts, revealing that mesocarp extract paradisi, whole C. sinesis, aurantinum, reticulata inhibited activity (IC50 values 5.79 ± 1.44 µg/mL, 37.19 5.92 42.62 6.89 57.65 3.81 respectively). Subsequent ESI-MSn analysis flavonoid, hesperidin, abundantly present all afore-mentioned extracts. Importantly, docking studies suggested hesperidin interacts residues, acts potent exhibiting IC50 value 11.34 3.83 µg/mL.A utilized evaluation Hesperidin, can serve could therapy 3a.