Journal
VIRUSES-BASEL
Volume 13, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/v13112118
Keywords
foot-and-mouth-disease virus (FMDV); luteolin; isoginkgetin; phytochemicals; FMDV 3C(pro); antiviral activity
Categories
Funding
- Thailand Science Research and Innovation (TSRI) [RTA6280011]
- Kasetsart University Research and Development Institute (KURDI) [FF(KU)17.64]
- Ministry of Education in Taiwan
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By utilizing computer-aided virtual screening of natural phytochemical compound libraries, the study identified luteolin and isoginkgetin as promising antiviral agents for FMDV. These compounds exhibited significant antiviral effects, particularly isoginkgetin which was found to be a potent inhibitor of FMDV 3C(pro). Further analysis suggested that both compounds interacted effectively with key enzymatic residues of the 3C(pro), indicating their potential for development as antiviral drugs against FMDV and other picornaviruses.
Foot-and-mouth-disease virus (FMDV) is a picornavirus that causes a highly contagious disease of cloven-hoofed animals resulting in economic losses worldwide. The 3C protease (3C(pro)) is the main protease essential in the picornavirus life cycle, which is an attractive antiviral target. Here, we used computer-aided virtual screening to filter potential anti-FMDV agents from the natural phytochemical compound libraries. The top 23 filtered compounds were examined for anti-FMDV activities by a cell-based assay, two of which possessed antiviral effects. In the viral and post-viral entry experiments, luteolin and isoginkgetin could significantly block FMDV growth with low 50% effective concentrations (EC50). Moreover, these flavonoids could reduce the viral load as determined by RT-qPCR. However, their prophylactic activities were less effective. Both the cell-based and the fluorescence resonance energy transfer (FRET)-based protease assays confirmed that isoginkgetin was a potent FMDV 3C(pro) inhibitor with a 50% inhibition concentration (IC50) of 39.03 & PLUSMN; 0.05 and 65.3 & PLUSMN; 1.7 mu M, respectively, whereas luteolin was less effective. Analyses of the protein-ligand interactions revealed that both compounds fit in the substrate-binding pocket and reacted to the key enzymatic residues of the 3C(pro). Our findings suggested that luteolin and isoginkgetin are promising antiviral agents for FMDV and other picornaviruses.
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