4.5 Review

Role of p38 mitogen-activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs

Journal

REVIEWS IN MEDICAL VIROLOGY
Volume 31, Issue 5, Pages -

Publisher

WILEY
DOI: 10.1002/rmv.2217

Keywords

MAPK; p38; signalling pathway; virus infection

Categories

Funding

  1. Science and Engineering Research Board [CRG/2018/004747, CRG/2019/000829, CVD/2020/000103]

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MAPKs play crucial roles in cellular processes, with p38 MAPK being activated by various cellular stresses and modulating downstream kinases and transcription factors. This pathway regulates functions such as cytoskeleton remodeling, cell cycle regulation, inflammation, antiviral response, and apoptosis.
Mitogen-activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal-related kinases (ERK)-1/2, p38 proteins, Jun amino-terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity.

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