The
COVID-19 crisis has emphasised the need for
antiviral therapies to combat current and future
viral zoonoses. Recent studies have shown that immune cells such as macrophages are the main contributors to the inflammatory response seen in the later inflammatory phase of
COVID-19. Immune cells in the context of a
viral infection such as SARS-CoV-2 undergo metabolic reprogramming to elicit these pro-inflammatory effector functions. The evidence of metabolic reprogramming in
COVID-19 offers opportunities for metabolites with immunomodulatory properties to be investigated as potential
therapies to combat this hyper-inflammatory response. Recent research indicates that the metabolite
itaconate, previously known to be broadly antibacterial, may have both
antiviral and immunomodulatory potential. Furthermore, low
itaconate levels have shown to correlate with
COVID-19 disease severity, potentially implicating its importance in the disease. The
antiviral potential of
itaconate has encouraged researchers to synthesise
itaconate derivatives for
antiviral screening, with some encouraging results. This review summarises the
antiviral and immunomodulatory potential of immunometabolic modulators including
metformin,
peroxisome proliferator-activated receptor agonists and
TEPP-46 as well as
itaconate, and its derivatives and their potential use as broad spectrum anti-viral agents.