File(s) not publicly available

Decoding the enigma of antiviral crisis: Does one target molecule regulate all?

journal contribution
posted on 12.03.2019, 00:00 by A Mahmud-Al-Rafat, A Majumder, KM Taufiqur Rahman, AM Mahedi Hasan, KM Didarul Islam, Andrew Taylor-RobinsonAndrew Taylor-Robinson, MM Billah
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. © 2018 Elsevier Ltd

History

Volume

115

Start Page

13

End Page

23

Number of Pages

11

eISSN

1096-0023

ISSN

1043-4666

Publisher

Academic Press, UK

Peer Reviewed

Yes

Open Access

No

Acceptance Date

03/12/2018

External Author Affiliations

University of Edinburgh; University of Ottawa, Canada; Hannover Medical School, Germany; Khulna University, Incepta Vaccine Ltd, Bangladesh;

Era Eligible

Yes

Journal

Cytokine