Targeting pivotal inflammatory pathways in COVID-19: A mechanistic review

As an emerging global health crisis, coronavirus disease 2019 (COVID-19) has been labeled a worldwide pandemic. Growing evidence is revealing further pathophysiological mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Amongst these dysregulated pathways inflammation seems to play a more critical role toward COVID-19 complications. In the present study, precise inflammatory pathways triggered by SARS-CoV-2, along with potential therapeutic candidates have been discussed. Prevailing evidence has indicated a close correlation of inflammatory cascades with severity, pathological progression, and organ damages in COVID-19 patients. From the mechanistic point of view, interleukin-6, interleukin-1β receptor, interferon-gamma, tumor necrosis factor-alpha receptor, toll-like receptor, receptor tyrosine kinases, growth factor receptor, Janus kinase/signal transducers and transcription pathway, mammalian target of rapamycin, cytokine storm and macrophage activation have shown to play critical roles in COVID-19 complications. So, there is an urgent need to provide novel mechanistic-based anti-inflammatory agents. This review highlights inflammatory signaling pathways of SARS-CoV-2. Several therapeutic targets and treatment strategies have also been provided in an attempt to tackle COVID-19 complications. Highlights • Inflammatory pathways are in a close linkage with COVID-19 complications. • Targeting IL-6, IL-1β receptor, TLR, IFN-γ, TNF-α and mTOR could pave the road in combating COVID-19. • JAK/STAT and related interconnected pathways are of pivotal pathways to be targeted in COVID-19. • PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and TRAF/TRADD/caspase could be promising targets in combating COVID-19.