Can concomitant use of zinc and curcumin with other immunity‐boosting nutraceuticals be the arsenal against COVID‐19?

Dear Editor, The recent pandemic spread of COVID-19 has socio-economically crippled the world and threatened humanity akin to World War II situation. The rise of this novel strain, SARS-CoV-2, and its exponential transmission rate have hindered the researchers to find a plausible prophylaxis and therapy to date. Therefore, slowing down the transmission rate is the only possible action plan. Thus, WHO recommended social distancing and improving personal hygiene as a protective measure, adhering to which, nations around the globe have imposed a total lockdown for its citizens. Aging and/or immunocompromised populations, as well as polymorbid patients, are the most vulnerable toward COVID-19, according to mortality and morbidity reports around the globe (Koff & Williams, 2020). It suggests that the COVID-19 has a proximate association with innate and adaptive immune responses, which declines with age and diseases. Further scientific investigations are warranted in these directions. However, the diet has an integrated role in raising our immune responses against pathogenic invasions. Adequate and proper nutrition is required for an “activated” immune system to meet the demand for energy during periods of infection. Micronutrients and dietary components play a specific role in the development and maintenance of an effective immune system, for example, Vitamin A and Zinc (Zn), via regulating cell division, which is involved in the proliferative response of the immune cells (Childs, Calder, & Miles, 2019). Whereas, Vitamin E is an antioxidant involved in the activation of protein kinase C. Similarly, prebiotic and probiotic-rich diets enrich the gut microbiota, which further nourishes the components of the immune system, such as immunoglobulin A (IgA). The majority of such immune cells reside in gut-associated lymphoid tissues, thus reflecting its importance in maintaining host health. Lack of effective prophylaxis against COVID-19 has prompted regulatory authorities to propose boosting of immunity of individuals via nutritional supplements. While modern medicine directly confronts an antigen (via vaccination or antibiotic), in comparison nutraceuticals, food supplements, and traditional medicines activate the overall immunity of the human body. To maintain optimum health during this lockdown period, recently, Ministry of AYUSH, Government of India, has also stressed upon various immunity-boosting steps concerning Ayurveda (AYUSH, 2020). Several suggestions from daily intake of warm water, Haldi, herbal tea, etc., to practicing yoga and Pranayama, have been suggested by the Indian Government. The hypothesis of Ayurveda or any other traditional system of medicine has been built around the concepts of practicing daily/seasonal regimes and consuming nutrients that further nourishes us and develops overall natural resistance against pathogens. US Food and Drug Administration (FDA) has already approved various food and immunity-boosting dietary supplements as safe (GRAS) level. Reports from China validate the use of Traditional Chinese Medicine (TCM) which has found success against COVID-19. A decoction of Qing Fei Pai Du (QPD), a TCM, has proven its effectivity in COVID-19 patients. Out of 701 confirmed cases treated by QPD, 130 cured cases, 51 cases with disappeared clinical symptoms, 268 cases of improved symptoms, and 212 cases of stable symptoms were found without aggravation (Ren, Zhang, & Wang, 2020). Thus, we can expand our discussion by taking the example of two nutritional supplements— Curcuminoids and Zn—which have been classified under GRAS, by FDA, as nutraceutical and nutrient. Both molecules have a proven history of antiviral activity in both in vitro and in vivo trials, and thus could be leading in developing new prophylactic candidates against COVID-19. Curcumin is a natural bioactive polyphenolic compound isolated from the dried powder of Curcuma longa rhizomes, commonly known as turmeric (Haldi in Hindi), and widely used worldwide for cooking. Ayurveda mentioned the use of turmeric for numerous therapeutic purposes like blood coagulation to immune stimulation. An array of systemic antioxidant properties has been attributed to curcumincontaining nutraceuticals. For example, it exerts an anti-inflammatory action in arthritis and inflammatory bowel diseases, reduces lipid levels in cardiovascular diseases, and addresses oxidative stress in skin disorders (Pagano, Romano, Izzo, & Borrelli, 2018). Curcumin has an established track record as an antiviral agent against several viruses like Influenza Type A, Hepatitis A, Zika, HIV, etc. The mode of action of curcumin includes—inhibition of viral entry into cells, suppression of viral replication, stimulation of interferons (IFNs) and other cytokines, and inhibition of viral protein expression. In silico studies have also revealed that curcumin binds directly with the receptor-binding domain of the viral spike protein (involved in host cell binding) and the cognate host cell receptor, angiotensin-converting enzyme-2 (serves as a medium of viral entry), of SARS-CoV-2 virus (Figure 1). Moreover, curcumin has been reported to inhibit the release and suppress numerous cytokines like IL-1β, IL-6, IL8, TNFα, MCP-1, etc. When investigated in various viral infections set-up, the mode of cytokine Received: 9 May 2020 Revised: 16 May 2020 Accepted: 18 May 2020