PLX8394, a RAF inhibitor, inhibits enterovirus 71 replication by blocking RAF/MEK/ERK signaling
Copyright © 2023 The Authors. Publishing services by Elsevier B.V. All rights reserved..
Enterovirus 71 (EV71) poses a serious threat to human health, with scattered outbreaks worldwide. There are several vaccines against a few EV71 strains but no efficient drug for the treatment of EV71 infection. Therefore, it is urgent and of significance to develop anti-EV71 drugs. Here, we found that PLX8394, a RAF inhibitor, possesses high antiviral activity against EV71 in vitro, being superior to the traditional clinical drug ribavirin. Moreover, PLX8394 exhibits broad-spectrum antiviral activity against enteroviruses. Notably, in a suckling mouse model, PLX8394 provided a 70% protection rate for EV71-infected mice, reduced the viral load in liver and heart tissues, and relieved the inflammatory response. A mechanistic study showed that PLX8394 inhibited EV71 by suppressing the RAF/MEK/ERK signaling pathway. Thus, PLX8394 lays a foundation for the development of new drugs against EV71.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Virologica Sinica - 38(2023), 2 vom: 12. Apr., Seite 276-284 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Chengyuan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.05.2023 Date Revised 15.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.virs.2023.01.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351804269 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Publishing services by Elsevier B.V. All rights reserved. | ||
| 520 | |a Enterovirus 71 (EV71) poses a serious threat to human health, with scattered outbreaks worldwide. There are several vaccines against a few EV71 strains but no efficient drug for the treatment of EV71 infection. Therefore, it is urgent and of significance to develop anti-EV71 drugs. Here, we found that PLX8394, a RAF inhibitor, possesses high antiviral activity against EV71 in vitro, being superior to the traditional clinical drug ribavirin. Moreover, PLX8394 exhibits broad-spectrum antiviral activity against enteroviruses. Notably, in a suckling mouse model, PLX8394 provided a 70% protection rate for EV71-infected mice, reduced the viral load in liver and heart tissues, and relieved the inflammatory response. A mechanistic study showed that PLX8394 inhibited EV71 by suppressing the RAF/MEK/ERK signaling pathway. Thus, PLX8394 lays a foundation for the development of new drugs against EV71 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antiviral agents | |
| 650 | 4 | |a Enterovirus 71 (EV71) | |
| 650 | 4 | |a Hand, foot, and mouth disease (HFMD) | |
| 650 | 4 | |a RAF inhibitor | |
| 650 | 4 | |a RAF/MEK/ERK signaling Pathway | |
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| 700 | 1 | |a Qiu, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Fuli |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Binbin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Qingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chaolin |e verfasserin |4 aut | |
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