Curcumin, a traditional spice component, can hold the promise against COVID-19?

Abstract

The severity of the recent pandemic and the absence of any specific medication impelled the identification of existing drugs with potential in the treatment of Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Curcumin, known for its pharmacological abilities especially as an anti-inflammatory agent, can be hypothesized as a potential candidate in the therapeutic regimen. COVID-19 has an assorted range of pathophysiological consequences, including pulmonary damage, elevated inflammatory response, coagulopathy, and multi-organ damage. This review summarizes the several evidences for the pharmacological benefits of curcumin in COVID-19-associated clinical manifestations. Curcumin can be appraised to hinder cellular entry, replication of SARS-CoV-2, and to prevent and repair COVID-19-associated damage of pneumocytes, renal cells, cardiomyocytes, hematopoietic stem cells, etc. The modulation and protective effect of curcumin on cytokine storm-related disorders are also discussed. Collectively, this review provides grounds for its clinical evaluation in the therapeutic management of SARS-CoV-2 infection.

Keywords: COVID-19; Curcumin; Cytokine storm; Inflammation; Molecular targets.

Graphical abstract

Fig. 1

Potential Targets of Curcumin in cellular entry and replication of SARAS-CoV-2. Curcumin can block the spike protein, ACE2, basigin, TMPRSS2, Furin, CatB/L, and inhibits endosomal acidification in order to prevent the cellular entry of SSARS-CoV-2. Curcumin may hinder the replication of SARS-CoV-2 through inhibition of RNA-dependent RNA polymerase (RdRp), Main Protease (M^Pro) and its release from infected cells.

Fig. 2

Modulation of Renin-Angiotensin System (RAS) by curcumin. Curcumin-mediated inhibition of ACE can decline the formation of AngII. Inactivation of AngII may be accelerated by curcumin-driven enhanced expression of ACE2. Curcumin can prevent the detrimental effects of AngII through the downregulation angiotensin AT₁ receptor. Stimulation of angiotensin AT₂ receptor and Mas receptor by Ang-(1–7) and Ang-(1–9), ACE2 catalyzed cleavage products of AngII and AngI, respectively, will also negate the effect of AngII.

Fig. 3

Promising targets of curcumin in cell signaling in COVID-19. Inhibition of AngII-stimulated angiotensin AT1 receptor signaling in COVID-19 by curcumin will hamper the activation of NF-κB and MCP-1. Curcumin will also inhibit the ADAM17 and prevent the formation of IL-6-sIL-6R complex and EGF. Enhanced degradation of EGFR and inhibition of mTOR by curcumin will also prevent ill effects in COVID-19. Inhibition of STAT3 by curcumin will also avoid the production of inflammatory cytokines.

Fig. 4

Inhibition of cytokine storm by curcumin in COVID-19. Viral components and cellular content released by infected cell lysis constitute PAMPs and DAMPs. PAMPs and DAMPs trigger TLR stimulation. Curcumin can inhibit TLR signaling and downstream activation of NF-κB, STAT3, and NLRP3 Inflammasome. This will prevent the production and elevated level of inflammatory cytokines, i.e. cytokine syndrome. This can avoid multiple organ damage in COVID-19.

Fig. 5

Potential of curcumin in COVID-19. Curcumin can affect various dimensions in COVID-19 including cellular entry and replication of SARS-CoV-2, Renin-Angiotensin system, cell signaling, and cytokine storm through their regulatory components. This will provide protection and repair of multi-organ injury.