Antiviral activity of silymarin and baicalein against dengue virus

Zhao Xuan Low,Brian Ming Ouyong,Babu Ramanathan,Pouya Hassandarvish,Chit Laa Poh

doi:10.1038/s41598-021-98949-y

Zhao Xuan Low, Brian Ming Ouyong + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-98949-y

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Abstract

Dengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral drug available currently. This study showed that flavonoids: silymarin and baicalein could inhibit the dengue virus in vitro and were well tolerated in Vero cells with a half-maximum cytotoxic concentration (CC50) of 749.70 µg/mL and 271.03 µg/mL, respectively. Silymarin and baicalein exerted virucidal effects against DENV-3, with a selective index (SI) of 10.87 and 21.34, respectively. Baicalein showed a better inhibition of intracellular DENV-3 progeny with a SI of 7.82 compared to silymarin. Baicalein effectively blocked DENV-3 attachment (95.59%) to the Vero cells, while silymarin prevented the viral entry (72.46%) into the cells, thus reducing viral infectivity. Both flavonoids showed promising antiviral activity against all four dengue serotypes. The in silico molecular docking showed that silymarin could bind to the viral envelope (E) protein with a binding affinity of − 8.5 kcal/mol and form hydrogen bonds with the amino acids GLN120, TRP229, ASN89, and THR223 of the E protein. Overall, this study showed that silymarin and baicalein exhibited potential anti-DENV activity and could serve as promising antiviral agents for further development against dengue infection.

Highlights

Compound Silymarin Baicalein Baicalin study showed that baicalin exhibited antiviral activity against EV-71 by suppressing the Fas/FasL pathway and 3D polymerase[16]
Based on the MNTD80 values, 200 μg/mL of silymarin, 100 μg/mL of baicalein, and 20 μg/mL of baicalin showed more than 80% cell viability and were chosen as the highest concentrations evaluated in the antiviral assays
The virucidal activity of flavonoids was evaluated in Fluorescence‐activated cell sorting (FACS) neutralization test (FNT), and the results showed that silymarin (200 μg/mL), baicalein (100 μg/mL), and baicalin (20 μg/mL) could neutralize 35.33%, 97.92%, and 31.91% of dengue virus (DENV)-3 infected cell’s population, respectively (Fig. 6)

Summary

Introduction

Compound Silymarin Baicalein Baicalin study showed that baicalin exhibited antiviral activity against EV-71 by suppressing the Fas/FasL pathway and 3D polymerase[16]. The anti-dengue potential of silymarin is unknown, and the inhibitory effects of baicalein and baicalin on other dengue serotypes have not been reported, with the exception of DENV-2. In this study, we aimed to determine the antiviral potential of silymarin, baicalein, and baicalin against DENV. Out of the three flavonoids investigated, silymarin and baicalein showed the potential to inhibit DENV-3, by direct extracellular virucidal action. We showed that silymarin and baicalein significantly interfered with DENV-3 attachment and entry to Vero cells, respectively. To our knowledge, this is the first study demonstrating the antiviral effects of silymarin and baicalein against all four dengue serotypes in vitro

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