Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro

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<sup>pro</sup>) is the main protease essential in the picornavirus life cycle, which is an attractive antivira...

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Autores principales:	Sirin Theerawatanasirikul, Nattarat Thangthamniyom, Chih-Jung Kuo, Ploypailin Semkum, Nantawan Phecharat, Penpitcha Chankeeree, Porntippa Lekcharoensuk
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	foot-and-mouth-disease virus (FMDV) luteolin isoginkgetin phytochemicals FMDV 3C<sup>pro</sup> antiviral activity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4eb329863d74494180130b0c7aeb7ca9
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spelling	oai:doaj.org-article:4eb329863d74494180130b0c7aeb7ca92021-11-25T19:12:24ZNatural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro10.3390/v131121181999-4915https://doaj.org/article/4eb329863d74494180130b0c7aeb7ca92021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2118https://doaj.org/toc/1999-4915Foot-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<sup>pro</sup>) 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 <i>viral</i> and <i>post-viral entry</i> 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<sup>pro</sup> inhibitor with a 50% inhibition concentration (IC50) of 39.03 ± 0.05 and 65.3 ± 1.7 μM, 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<sup>pro</sup>. Our findings suggested that luteolin and isoginkgetin are promising antiviral agents for FMDV and other picornaviruses.Sirin TheerawatanasirikulNattarat ThangthamniyomChih-Jung KuoPloypailin SemkumNantawan PhecharatPenpitcha ChankeereePorntippa LekcharoensukMDPI AGarticlefoot-and-mouth-disease virus (FMDV)luteolinisoginkgetinphytochemicalsFMDV 3C<sup>pro</sup>antiviral activityMicrobiologyQR1-502ENViruses, Vol 13, Iss 2118, p 2118 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	foot-and-mouth-disease virus (FMDV) luteolin isoginkgetin phytochemicals FMDV 3C<sup>pro</sup> antiviral activity Microbiology QR1-502
spellingShingle	foot-and-mouth-disease virus (FMDV) luteolin isoginkgetin phytochemicals FMDV 3C<sup>pro</sup> antiviral activity Microbiology QR1-502 Sirin Theerawatanasirikul Nattarat Thangthamniyom Chih-Jung Kuo Ploypailin Semkum Nantawan Phecharat Penpitcha Chankeeree Porntippa Lekcharoensuk Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro
description	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<sup>pro</sup>) 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 <i>viral</i> and <i>post-viral entry</i> 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<sup>pro</sup> inhibitor with a 50% inhibition concentration (IC50) of 39.03 ± 0.05 and 65.3 ± 1.7 μM, 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<sup>pro</sup>. Our findings suggested that luteolin and isoginkgetin are promising antiviral agents for FMDV and other picornaviruses.
format	article
author	Sirin Theerawatanasirikul Nattarat Thangthamniyom Chih-Jung Kuo Ploypailin Semkum Nantawan Phecharat Penpitcha Chankeeree Porntippa Lekcharoensuk
author_facet	Sirin Theerawatanasirikul Nattarat Thangthamniyom Chih-Jung Kuo Ploypailin Semkum Nantawan Phecharat Penpitcha Chankeeree Porntippa Lekcharoensuk
author_sort	Sirin Theerawatanasirikul
title	Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro
title_short	Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro
title_full	Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro
title_fullStr	Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro
title_full_unstemmed	Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro
title_sort	natural phytochemicals, luteolin and isoginkgetin, inhibit 3c protease and infection of fmdv, in silico and in vitro
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4eb329863d74494180130b0c7aeb7ca9
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Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro

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