Potential Regulation of NF-κB by Curcumin in Coronavirus-Induced Cytokine Storm and Lung Injury

The current pandemic coronavirus disease-19 (COVID-19) is still a global medical and economic emergency with over 244 million confirmed infections and over 4.95 million deaths by October 2021, in less than 2 years. Severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome coronavirus (MERS), and COVID-19 are three recent coronavirus pandemics with major medical and economic implications. Currently, there is no effective treatment for these infections. One major pathological hallmark of these infections is the so-called ‘cytokine storm,’ which depicts an unregulated production of inflammatory cytokines inducing detrimental inflammation leading to organ injury and multiple organ failure including severe pulmonary, cardiovascular, and kidney failure in COVID-19. Several studies have suggested the potential of curcumin to inhibit the replication of some viruses similar to coronaviruses. Multiple experimental and clinical studies also reported the anti-inflammatory potential of curcumin in multiple infectious and inflammatory disorders. Thus, we hypothesized that curcumin may provide antiviral and anti-inflammatory effects for treating COVID-19. Although these studies suggest that curcumin could serve as an adjuvant treatment for COVID-19, its molecular mechanisms are still debated, especially its potential to modulate the toll-like receptors/TIR-domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR/TRIF/NF-κB) pathway. The preliminary results showed that curcumin modulates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, a common pathway controlling cytokine production in multiple infectious and inflammatory disorders. Here, we hypothesize and discuss whether curcumin treatment may provide antiviral and anti-inflammatory clinical advantages for treating COVID-19 by modulating the TLR/TRIF/NF-κB pathway. We also review the current data on curcumin and discuss potential experimental and clinical studies that require defining its potential clinical implications in COVID-19.