Decoding the enigma of antiviral crisis : Does one target molecule regulate all?
Copyright © 2018 Elsevier Ltd. All rights reserved..
Disease fatality associated with Ebola, SARS-CoV and dengue infections in humans is attributed to a cytokine storm that is triggered by excessive pro-inflammatory responses. Interleukin (IL)-6 acts as a mediator between pro- and anti-inflammatory reactivity by initiating trans- and classical-signaling, respectively. Hence, IL-6 is assumed to provide a target for a broad range of antiviral agents. Available immunosuppressive antivirals are directed to control an often exaggerated pro-inflammatory response that gives rise to complex clinical conditions such as lymphocytopenia. It is known that IL-6, via its soluble receptor (sIL-6R), initiates a pro-inflammatory response while an anti-inflammatory response is triggered by the membrane-bound IL-6 receptor (IL-6R). Future antivirals should thus aim to target the mechanism that regulates switching between IL-6 trans- and classical-signaling. In this review, we propose that the tumour necrosis factor-α converting enzyme ADAM-17 could be the master molecule involved in regulating IL-6 class switching and through this in controlling pro- and anti-inflammatory responses to viral antigenic stimuli. Therefore, ADAM-17 should be considered as a potential target molecule for novel antiviral drug discovery that would regulate host reactivity to infection and thereby limit or prevent fatal outcomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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| Enthalten in: |
Cytokine - 115(2019) vom: 15. März, Seite 13-23 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mahmud-Al-Rafat, Abdullah [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.04.2020 Date Revised 23.04.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cyto.2018.12.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM292445784 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Disease fatality associated with Ebola, SARS-CoV and dengue infections in humans is attributed to a cytokine storm that is triggered by excessive pro-inflammatory responses. Interleukin (IL)-6 acts as a mediator between pro- and anti-inflammatory reactivity by initiating trans- and classical-signaling, respectively. Hence, IL-6 is assumed to provide a target for a broad range of antiviral agents. Available immunosuppressive antivirals are directed to control an often exaggerated pro-inflammatory response that gives rise to complex clinical conditions such as lymphocytopenia. It is known that IL-6, via its soluble receptor (sIL-6R), initiates a pro-inflammatory response while an anti-inflammatory response is triggered by the membrane-bound IL-6 receptor (IL-6R). Future antivirals should thus aim to target the mechanism that regulates switching between IL-6 trans- and classical-signaling. In this review, we propose that the tumour necrosis factor-α converting enzyme ADAM-17 could be the master molecule involved in regulating IL-6 class switching and through this in controlling pro- and anti-inflammatory responses to viral antigenic stimuli. Therefore, ADAM-17 should be considered as a potential target molecule for novel antiviral drug discovery that would regulate host reactivity to infection and thereby limit or prevent fatal outcomes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a ADAM-17 | |
| 650 | 4 | |a Antiviral | |
| 650 | 4 | |a Cytokine storm | |
| 650 | 4 | |a Dengue | |
| 650 | 4 | |a Ebola | |
| 650 | 4 | |a IL-6 | |
| 650 | 4 | |a Pro-inflammatory response | |
| 650 | 4 | |a SARS-CoV | |
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| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
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| 700 | 1 | |a Majumder, Apurba |e verfasserin |4 aut | |
| 700 | 1 | |a Taufiqur Rahman, K M |e verfasserin |4 aut | |
| 700 | 1 | |a Mahedi Hasan, A M |e verfasserin |4 aut | |
| 700 | 1 | |a Didarul Islam, K M |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor-Robinson, Andrew W |e verfasserin |4 aut | |
| 700 | 1 | |a Billah, Md Morsaline |e verfasserin |4 aut | |
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