Coronavirus disease 2019 (COVID-19) is an infectious disease that rapidly spread throughout the world leading to high mortality rates. Despite the knowledge of previous diseases caused by viruses of the same family, such as MERS and SARSCoV, management and treatment of patients with COVID-19 is a challenge. One of the best strategies around the world to help combat the COVID-19 has been directed to drug repositioning; however, these drugs are not specific to this new virus. Additionally, the pathophysiology of COVID-19 is highly heterogeneous, and the way of SARS-CoV-2 modulates the different systems in the host remains unidentified, despite recent discoveries. This complex and multifactorial response requires a comprehensive therapeutic approach, enabling the integration and refinement of therapeutic responses of a given single compound that has several action potentials. In this context, natural compounds, such as Curcumin, have shown beneficial effects on the progression of inflammatory diseases due to its numerous action mechanisms: antiviral, antiinflammatory, anticoagulant, antiplatelet, and cytoprotective. These and many other effects of curcumin make it a promising target in the adjuvant treatment of COVID-19. Hence, the purpose of this review is to specifically point out how curcumin could interfere at different times/points during the infection caused by SARS-CoV-2, providing a substantial contribution of curcumin as a new adjuvant therapy for the treatment of COVID-19.
Introduction
Coronavirus disease 19 (COVID-19/2019-nCoV) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestation of COVID-19 range from asymptomatic upper respiratory tract infection to critical illness and pneumonia associated with acute respiratory distress syndrome (ARDS) (Guan et al., 2020). The main risk factors associated with greater severity and mortality caused by COVID-19 include hypertension, diabetes mellitus, cardiovascular disease (CVD), advanced age, and obesity (Simonnet et al., 2020; Wu and McGoogan, 2020; Zhou et al., 2020).
SARS-CoV-2 is an enveloped β-coronavirus composed of four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins (Chen et al., 2020). Entry of the virus into the host cell occurs through the cleavage of protein S into two subunits (S1 and S2) where SARSCoV- 2 develops a multibasic site at the S1-S2 boundary, which is cleaved by furin to form protein S for processing by TMPRSS2 (Hoffmann et al., 2020). The amino-terminal S1 subunit contains a receptor-binding domain (RBD) that is responsible for binding to the cell surface receptor, angiotensin-converting enzyme 2 (ACE2) (Wrapp et al., 2020; Xia et al., 2020). The membrane anchored S2 subunit is composed of the fusion peptide (FP), heptapeptide repeat sequences 1 and 2 (HR1/HR2), transmembrane domain (TM), and cytoplasmic domain. These components are responsible for viral fusion and cell invasion (Huang Y. et al., 2020; Xia et al., 2020). After the RBD domain is attached to ACE2, the S2 subunit changes its conformation and moves closer to the viral envelope and cell membrane for viral fusion and entry (Huang Y. et al., 2020). In the host, ACE2 is widely expressed in the lungs, heart, liver, vascular endothelium, kidneys, and gut. It is an important regulator of the reninangiotensin- aldosterone system (RAAS), and promotes the conversion of angiotensin I (Ang I) to Ang (1–9) and Ang II to Ang (1–7) (D’ardes et al., 2020; Gheblawi et al., 2020). Ang (1–7) has an important physiological role and promotes vasodilation, including anti-hypertrophic, anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-fibrotic effects (Imai et al., 2005; Kuba et al., 2005; Chung et al., 2020; D’ardes et al., 2020). The conversion of Ang II to Ang (1–7) regulates the concentration of Ang II-mediated by ACE2. When available, Ang II binds to the ATR1 receptor, thereby promoting harmful pro-inflammatory effects, such as hypertrophy, oxidative stress, and vasoconstriction (Imai et al., 2005; Kuba et al., 2005; Chung et al., 2020; D’ardes et al., 2020). Therefore, the negative regulation of ACE2, promoted by the binding of SARS-CoV-2, results in increased levels of Ang II (Imai et al., 2005; Kuba et al., 2005; D’ardes et al., 2020).