Antiviral activity of flavonoids: Silymarin, Baicalein, and Baicalin against dengue virus

Low, Zhao Xuan (2021) Antiviral activity of flavonoids: Silymarin, Baicalein, and Baicalin against dengue virus. Masters thesis, Sunway University.

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Dengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral treatment. It was estimated that 390 million cases of dengue cases were reported yearly with 500000 hospitalization and 25000 deaths. Dengue is caused by dengue virus (DENV) which was subcategorized into four groups, DENV1-4. The FDA approved tetravalent Dengvaxia vaccine is approved for use in few countries against all four dengue serotypes. However, the vaccine has showed low efficacy against serotypes 1 and 2. Hence, there is an urgent requirement for an effective antiviral drug effective against all four dengue serotypes This study investigated the antiviral activity of flavonoids: silymarin, baicalein and baicalin against dengue virus (DENV) in vitro. The cytotoxicity effect of flavonoids on Vero cells was first examined using an MTS assay and was found that silymarin, baicalein, and baicalin were tolerable on Vero cells with half-maximum cytotoxic concentration (CC50) of 749.70, 271.03, and 54.64 μg/mL, respectively. These flavonoids were then evaluated for their in vitro antiviral activity against DENV-3 sub-genotype H87 at their non-cytotoxic concentrations using various antiviral assays. Viral infectivity was determined through foci-forming unit reduction assay (FFURA), real-time quantitative reverse transcription PCR (qRT-PCR), and FACS neutralization test (FNT). The mode of inhibition of flavonoids was then further evaluated through time course, virus attachment, and entry assays. Silymarin and baicalein were shown to exert significant virucidal effects against all four dengue serotypes. Silymarin and baicalein inactivated extracellular DENV-3 particles, with SI of 10.87 and 21.34, respectively. Baicalein but not silymarin showed a post-infection effect against DENV-3 with an SI of 7.82. Besides that, baicalein effectively blocked the viral attachment (95.59%) to the host cells, while silymarin prevented the viral entry (72.46%) into Vero cells, thus reducing the viral infectivity. The in silico molecular docking showed that silymarin could bind to the E protein with a binding affinity of -8.5 Kcal/mol and form hydrogen bonds with GLN120, TRP229, ASN89, and THR223 residues of dengue E protein. Overall, this study showed that silymarin and baicalein exhibited promising anti-dengue activity and could serve as promising antiviral agents to treat dengue infection.

Item Type: Thesis (Masters)
Uncontrolled Keywords: antiviral activity; flavonoids; Silymarin; Baicalein; Baicalin.
Subjects: R Medicine > RA Public aspects of medicine
R Medicine > RC Internal medicine
R Medicine > RM Therapeutics. Pharmacology
Divisions: Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020]
Depositing User: Ms Yong Yee Chan
Date Deposited: 08 Oct 2023 23:42
Last Modified: 08 Oct 2023 23:42

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