Antiviral activity of the HSP90 inhibitor VER-50589 against enterovirus 71
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
Enterovirus 71 (EV71) is the major pathogen responsible for hand, foot, and mouth disease (HFMD) outbreaks; to date, there is no specific anti-EV71 agent. HSP90 is a crucial host factor for the viral life cycle and an ideal therapeutic target for limiting viral proliferation. However, the specific role of HSP90 in EV71-related signaling pathways and anti-EV71 agents targeting HSP90 remains unclear. This study aimed to verify the role of HSP90 in signaling pathways involved in EV71 replication and investigate the antiviral effects of a small molecule of VER-50589, a potent HSP90 inhibitor, against EV71 both in vitro and in vivo. Viral plaque assay, western blotting, and qPCR results showed that VER-50589 diminished the plaque formation induced by EV71 and inhibited EV71 mRNA and protein synthesis. A single daily dose of VER-50589 treatment significantly improved the survival rate of EV71-infected mice (p < 0.005). Interestingly, VER-50589 also exhibits activities against a series of human enteroviruses, including Coxsackievirus B3 (CVB3), Coxsackievirus B4-5 (CVB4-5), Coxsackievirus B4-7 (CVB4-7), and Echovirus 11 (Echo11). EV71 infection activated the AKT and ERK signaling pathways, and phosphorylation of AKT and RAF/MEK/ERK was weakened by VER-50589 administration. Thus, VER-50589 exhibits robust antiviral activity by inhibiting HSP90 and mediating the AKT and RAF/MEK/ERK signaling pathways. Considering that there are no effective antivirals or vaccines for the prevention and cure of HFMD in a clinical setting, the development of an anti-EV71 agent would be a straightforward and feasible therapeutic approach.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:211 |
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| Enthalten in: |
Antiviral research - 211(2023) vom: 15. März, Seite 105553 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Guangyan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.02.2023 Date Revised 16.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2023.105553 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Antiviral activity of the HSP90 inhibitor VER-50589 against enterovirus 71 |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Enterovirus 71 (EV71) is the major pathogen responsible for hand, foot, and mouth disease (HFMD) outbreaks; to date, there is no specific anti-EV71 agent. HSP90 is a crucial host factor for the viral life cycle and an ideal therapeutic target for limiting viral proliferation. However, the specific role of HSP90 in EV71-related signaling pathways and anti-EV71 agents targeting HSP90 remains unclear. This study aimed to verify the role of HSP90 in signaling pathways involved in EV71 replication and investigate the antiviral effects of a small molecule of VER-50589, a potent HSP90 inhibitor, against EV71 both in vitro and in vivo. Viral plaque assay, western blotting, and qPCR results showed that VER-50589 diminished the plaque formation induced by EV71 and inhibited EV71 mRNA and protein synthesis. A single daily dose of VER-50589 treatment significantly improved the survival rate of EV71-infected mice (p < 0.005). Interestingly, VER-50589 also exhibits activities against a series of human enteroviruses, including Coxsackievirus B3 (CVB3), Coxsackievirus B4-5 (CVB4-5), Coxsackievirus B4-7 (CVB4-7), and Echovirus 11 (Echo11). EV71 infection activated the AKT and ERK signaling pathways, and phosphorylation of AKT and RAF/MEK/ERK was weakened by VER-50589 administration. Thus, VER-50589 exhibits robust antiviral activity by inhibiting HSP90 and mediating the AKT and RAF/MEK/ERK signaling pathways. Considering that there are no effective antivirals or vaccines for the prevention and cure of HFMD in a clinical setting, the development of an anti-EV71 agent would be a straightforward and feasible therapeutic approach | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Antiviral activity | |
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| 700 | 1 | |a Wu, Chengyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Danchun |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Binbin |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xujuan |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhengnan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chaolin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Qingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dingyu |e verfasserin |4 aut | |
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