The Efficacies of Curcumin in treating COVID-19

Introduction:

Coronavirus disease-19 (COVID-19) is a devastating respiratory illness and has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection. Prophylactic therapeutics (medication/treatment used to prevent a disease from occurring) for COVID-19 are being developed by various companies.

Curcumin, a bioactive compound in turmeric exhibits evidence of a promising prophylactic therapeutic candidate for COVID-19. This study reviews several line of evidence in this accordance.

First, curcumin exerts antiviral activity against many types of enveloped viruses, including SARS-CoV-2, by multiple mechanisms:

• direct interaction with viral membrane proteins;
• disruption of the viral envelope;
• inhibition of viral proteases;
• induce host antiviral responses.

Second, curcumin protects from lethal pneumonia and ARDS via targeting NF-κB, inflammasome, IL-6 trans signal, and HMGB1 pathways.

Third, curcumin is safe and well-tolerated in both healthy and diseased human subjects.

Accumulated evidence indicates that curcumin may be a potential prophylactic therapeutic for COVID-19 in the clinic and public health settings.

Curcumin has been proven to have antiviral effects against enveloped viruses, which cause human diseases like- SARS-CoV, Influenza A virus, Respiratory syncytial virus, Herpes simplex virus, Japanese encephalitis virus, HIV, Hepatitis B & C virus, Zika, Chikungunya virus, Dengue virus

Immunomodulatory activity of curcumin suppress cytokine release syndrome (CRS) and mitigates progression to Acute respiratory distress syndrome (ARDS). The death of severely ill COVID-19 patients is associated with respiratory failure and or multiorgan failure caused by Acute respiratory distress syndrome (ARDS) and septic shock. ARDS and or sepsis's pathogenesis involves an early hyperactivated inflammatory response characterized by a "cytokine storm" (Chen et al., 2020a, 2020c). A positive association between cytokine release syndrome (CRS) and the severity of illness and mortality among COVID-19 patients is reported by many studies (Tang et al., 2020). Immunomodulatory drugs are likely to effectively mitigate ARDS progression or sepsis by dampening early inflammatory response following infectious insults (Tang et al., 2020; Yadav et al., 2017).

The schematics representing the potential mechanisms by which curcumin may be effective against COVID-19 (A) Antiviral activity of curcumin against SARS-CoV-2 mediated by disrupting the viral envelope, S protein and or ACE2, which prevents the entry of the virus into the cells. B. Curcumin induces antiviral responses by positively regulating NRF2 and repressing ACE2 expression by negatively regulating HMGB1. C. Curcumin mediates immunomodulatory responses by inhibiting cytokine response syndrome and oxidative stress and thus mitigating the progression to pneumonia and or Acute respiratory distress syndrome (ARDS) following SARS-CoV-2 infection.

Administration of Curcumin for treating COVID-19

Broad-spectrum antiviral activity and immunomodulatory activity provides a strong rationale for testing curcumin for COVID-19 treatment. However, low bioavailability is the major obstacle in attaining the therapeutic potential of oral curcumin. In contrast, pulmonary delivery of curcumin will overcome this limitation and offers several advantages:

• direct delivery of high concentration of curcumin to the site of infection;
• direct contact of curcumin with the virus SARS-CoV-2;
• direct deposition into lower airways and alveolar region;
• larger surface area for deposition and absorption;
• lower intra- and extracellular detoxification enzymatic activity in the pulmonary system (Borghardt et al., 2018).

In summary, accumulated evidence suggests that the pulmonary delivery of nanoformulated curcumin such as liposomal curcumin would help in deposition of curcumin in the lower airways at a higher concentration, which may inhibit SARS-CoV-2 infectivity and concomitantly mitigate pulmonary inflammation and the progression to ARDS.

Conclusions

There is an urgent need for therapeutics against COVID-19 outbreak. Besides vaccine trials, few therapeutics such as remdesivir and or interferon-beta based on prior knowledge of antiviral activity against SARS-CoV, are in clinical practice for the treatment of COVID-19. Recognizing the public health emergency, perhaps it is imperative to evaluate phytochemical curcumin for management or treatment of COVID-19 in a randomized clinical trial because

1. it is relatively safe;
2. it shows broad-spectrum antiviral activity against enveloped viruses;
3. it may suppress SARS-CoV-2 infection by directly modifying spike protein and or ACE2 and inducing host antiviral responses by targeting NRF2 and HMGB1;
4. it exerts immunomodulatory activity by blocking NF-κB, inflammasome, HMGB1, and IL-6 driven inflammatory responses;
5. it dampens ROS production by inhibiting NADPH oxidase and alleviates oxidative tissue injury by increasing antioxidant defenses by modulating NRF2.

To read the detailed study, please click here