Pralatrexate inhibited the replication of varicella zoster virus and vesicular stomatitis virus : An old dog with new tricks
Copyright © 2023 Elsevier B.V. All rights reserved..
Varicella zoster virus (VZV) is associated with herpes zoster (HZ) or herpes zoster ophthalmicus (HZO). All antiviral agents currently licensed for the management of VZV replication via modulating different mechanisms, and the resistance is on the rise. There is a need to develop new antiviral agents with distinct mechanisms of action and adequate safety profiles. Pralatrexate (PDX) is a fourth-generation anti-folate agent with an inhibitory activity on folate (FA) metabolism and has been used as an anti-tumor drug. We observed that PDX possessed potent inhibitory activity against VZV infection. In this study, we reported the antiviral effects and the underlying mechanism of PDX against VZV infection. The results showed that PDX not only inhibited VZV replication in vitro and in mice corneal tissues but also reduced the inflammatory response and apoptosis induced by viral infection. Furthermore, PDX treatment showed a similar anti-VSV inhibitory effect in both in vitro and in vivo models. Mechanistically, PDX inhibited viral replication by interrupting the substrate supply for de novo purine and thymidine synthesis. In conclusion, this study discovered the potent antiviral activity of PDX with a novel mechanism and presented a new strategy for VZV treatment that targets a cellular metabolic mechanism essential for viral replication. The present study provided a new insight into the development of broad-spectrum antiviral agents.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:221 |
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| Enthalten in: |
Antiviral research - 221(2024) vom: 01. Jan., Seite 105787 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Jing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.01.2024 Date Revised 22.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2023.105787 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Wu, Jing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pralatrexate inhibited the replication of varicella zoster virus and vesicular stomatitis virus |b An old dog with new tricks |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a Varicella zoster virus (VZV) is associated with herpes zoster (HZ) or herpes zoster ophthalmicus (HZO). All antiviral agents currently licensed for the management of VZV replication via modulating different mechanisms, and the resistance is on the rise. There is a need to develop new antiviral agents with distinct mechanisms of action and adequate safety profiles. Pralatrexate (PDX) is a fourth-generation anti-folate agent with an inhibitory activity on folate (FA) metabolism and has been used as an anti-tumor drug. We observed that PDX possessed potent inhibitory activity against VZV infection. In this study, we reported the antiviral effects and the underlying mechanism of PDX against VZV infection. The results showed that PDX not only inhibited VZV replication in vitro and in mice corneal tissues but also reduced the inflammatory response and apoptosis induced by viral infection. Furthermore, PDX treatment showed a similar anti-VSV inhibitory effect in both in vitro and in vivo models. Mechanistically, PDX inhibited viral replication by interrupting the substrate supply for de novo purine and thymidine synthesis. In conclusion, this study discovered the potent antiviral activity of PDX with a novel mechanism and presented a new strategy for VZV treatment that targets a cellular metabolic mechanism essential for viral replication. The present study provided a new insight into the development of broad-spectrum antiviral agents | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Folate metabolism | |
| 650 | 4 | |a Herpes zoster ophthalmicus | |
| 650 | 4 | |a Pralatrexate | |
| 650 | 4 | |a Varicella zoster virus | |
| 650 | 4 | |a Vesicular stomatitis virus | |
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| 700 | 1 | |a Jiang, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Yajie |e verfasserin |4 aut | |
| 700 | 1 | |a Lyu, Ruining |e verfasserin |4 aut | |
| 700 | 1 | |a You, Qiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Hongji |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Haotian |e verfasserin |4 aut | |
| 700 | 1 | |a Nawaz, Waqas |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Deyan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Zhiwei |e verfasserin |4 aut | |
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