Andrographolide and Deoxyandrographolide Inhibit Protease and IFN-Antagonist Activities of Foot-and-Mouth Disease Virus 3Cpro

Sirin Theerawatanasirikul; Varanya Lueangaramkul; Nattarat Thangthamniyom; Penpitcha Chankeeree; Ploypailin Semkum; Porntippa Lekcharoensuk

doi:10.3390/ani12151995

Andrographolide and Deoxyandrographolide Inhibit Protease and IFN-Antagonist Activities of Foot-and-Mouth Disease Virus 3C^pro

Animals (Basel). 2022 Aug 7;12(15):1995. doi: 10.3390/ani12151995.

Authors

Sirin Theerawatanasirikul¹, Varanya Lueangaramkul², Nattarat Thangthamniyom², Penpitcha Chankeeree², Ploypailin Semkum², Porntippa Lekcharoensuk^{2

3}

Affiliations

¹ Department of Anatomy, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand.
² Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand.
³ Center for Advanced Studies in Agriculture and Food, Kasetsart University Institute for Advanced Studies, Kasetsart University, Bangkok 10900, Thailand.

Abstract

Foot-and mouth-disease (FMD) caused by the FMD virus (FMDV) is highly contagious and negatively affects livestock worldwide. The control of the disease requires a combination of measures, including vaccination; however, there is no specific treatment available. Several studies have shown that plant-derived products with antiviral properties were effective on viral diseases. Herein, antiviral activities of andrographolide (AGL), deoxyandrographolide (DAG), and neoandrographolide (NEO) against FMDV serotype A were investigated using an in vitro cell-based assay. The results showed that AGL and DAG inhibited FMDV in BHK-21 cells. The inhibitory effects of AGL and DAG were evaluated by RT-qPCR and exhibited EC50 values of 52.18 ± 0.01 µM (SI = 2.23) and 36.47 ± 0.07 µM (SI = 9.22), respectively. The intracellular protease assay revealed that AGL and DAG inhibited FMDV 3C^pro with IC50 of 67.43 ± 0.81 and 25.58 ± 1.41 µM, respectively. Additionally, AGL and DAG significantly interfered with interferon (IFN) antagonist activity of the 3C^pro by derepressing interferon-stimulating gene (ISGs) expression. The molecular docking confirmed that the andrographolides preferentially interacted with the 3C^pro active site. However, NEO had no antiviral effect in any of the assays. Conclusively, AGL and DAG inhibited FMDV serotype A by interacting with the 3C^pro and hindered its protease and IFN antagonist activities.

Keywords: 3C protease (3Cpro); andrographolide; antiviral activity; deoxyandrographolide; diterpenoids; foot-and-mouth disease virus; intracellular protease inhibitory assay; molecular docking.

Abstract

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