Review on selected potential nutritional intervention for treatment and prevention of viral infections: possibility of recommending these for Coronavirus 2019

ABSTRACT

An outbreak of a novel coronavirus (COVID-19) infection has posed significant threats to international health and the economy. The role of nutrition in supporting the immune system is well-established. A wealth of mechanistic and clinical documents shows that vitamins, including vitamins A, B2, B3, B6, B12, C, D, E, and folate; trace elements, including zinc and selenium; probiotics and prebiotics; alpha lipoic acid; omega-3 fatty acids and herbal supplements including curcumin, ginger, Echinacea, garlic, green tea, cinnamon, and ginseng play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: (1) supplementation with the above micronutrients, omega-3 fatty acids, and probiotics is a safe, effective, and low-cost strategy to help support optimal immune function; (2) supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C, D, and selenium is warranted; and (3) public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

KEYWORDS:

• Coronavirus
• COVID-19
• 2019-CoV
• nutrition

Introduction

In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found in Wuhan, China, and infections spread across China and other countries around the world.^[1] The World Health Organization (WHO) announced the novel coronavirus as Coronavirus Disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) and it spread worldwide with as a pandemic .^[2,3] Even more, the COVID-19 pandemic has a considerable influence on the economy worldwide .^[4]

Coronaviruses belong to the subfamily Orthocoronavirinae in the family of Coronaviridae and the order Nidovirales, have an enveloped, crown-like viral particle from which they were named after .^[3,5] Coronaviruses can cause illnesses such as the common cold, severe acute respiratory syndrome (SARS-CoV), and the Middle East respiratory syndrome (MERS-CoV). Coronaviruses primarily have been identified as the causes of enzootic infections in birds and mammals and, in the last decades, have been implicated as a possible cause of infecting humans .^[3,5–7]

Nutritional homeostasis is a key factor in improving the immune system and essential nutrients deficiencies can lead to poor immune function and predisposition to infections .^[8,9] Currently, there is no FDA-approved vaccine for this novel virus. Therefore, finding a therapeutic agent for preventing or controlling and treating the virus is urgent. In the present study, we tried to review studies that investigated the effect of nutritional factors on immune response and viral infection specially coronavirus.

Vitamins

Vitamin A

Vitamin A is an essential fat-soluble vitamin that is found naturally only in animal products and its plant-derived precursor (beta-carotene), found primarily in foods of plant origin .^[10] Human immune defense against infection relies on an adequate supply of vitamin A, also called “anti-infective” which is 900 retinol activity equivalent (RAE) for men and 700 RAE for women .^[5] Previously, it has been proven that vitamin A deficiency leading to diarrhea^[11] and measles, a respiratory tract viral infection, and measles could be more severe in vitamin-A deficient individuals .^[12] Semba and colleagues, ^[13] had documented that supplementation with vitamin A could reduce morbidity and mortality in different infectious diseases, like measles, diarrheal disease, measles-related pneumonia, human immunodeficiency virus (HIV) infection, and malaria. Jee et al.^[14] had proposed that a low vitamin A diet compromised the serum Immunoglobulin G1 (IgG1) responses against inactivated bovine coronavirus vaccine, which suggested suppressed T-helper 2–associated antibody responses. On the other hand, viral vaccines are less effective and calves are more prone to infectious diseases when there is vitamin A deficiency. Additionally, infectious bronchitis virus (IBV), a kind of coronavirus, established more pronounced infection in chickens fed a deficient vitamin A diet compared to those with adequate vitamin A diet .^[15] Measles virus could inhibit type 1 interferon (IFN) signaling, an antiviral innate immunity. IFN-stimulated genes are up-regulated by all-trans retinoic acid in infected and uninfected cells which makes them intractable to a subsequent round of viral replication .^[16] Besides, bioinformatics findings revealed that the mechanisms of action of vitamin A against COVID-19 include enrichment of immunoreaction, inhibition of inflammatory reaction, and biological processes related to reactive oxygen species. Furthermore, seven core targets of VA against COVID-19, including MAPK1, IL10, EGFR, ICAM1, MAPK14, CAT, and PRKCB were identified .^[17] Therefore, vitamin A could be a hopeful option for the prevention and treatment of COVID-19 and subsequent lung infection as its role in immune system boosting .^[18] While, there is no consensus regarding the dosage of vitamin A supplementation, providing the recommended dietary allowance (RDA) seems to be a practical approach.

B vitamins

B vitamins are categorized as water-soluble vitamins and play a crucial role as parts of coenzymes. Each B vitamins has its especial function in different biochemical pathways. In 2016, Keil et al. had stated that riboflavin and ultraviolet light-based photochemical treatment effectively reduced the titer of MERS-CoV in human plasma products below the detection limit .^[19] Besides, nicotinamide treatment significantly hindered neutrophil infiltration into the lungs during ventilator-induced lung injury but did not affect protein leakage or cytokine production. However, nicotinamide treated mice developed significantly worse hypoxemia through mechanical ventilation, surprisingly .^[20] As reported by Im et al., no significant increase for vitamin B1, B6, B12, and folate deficiency were observed among 50 hospitalized patients with COVID-19 .^[21] As B vitamins deficiency may deteriorate host immune response, COVID-19 patients supplementation could be kept in mind to enhance their immune system in case of deficiency .^[22]

Vitamin C

Vitamin C (Ascorbic acid) is another water-soluble vitamin that means “no-scurvy acid”. Anti-oxidant activity and synthesis of collagen in connective tissues were contributed to vitamin C. Also, vitamin C could up-regulate the immune system by the function of phagocytes, a transformation of T lymphocytes, and production of interferon^[23] and could be considered for protection against coronavirus infection .^[24] Particularly, vitamin C increased the resistance of chick embryo tracheal organ cultures to infection of avian coronavirus .^[25] Davelaar et al. had reported that vitamin C could protect broiler chicks against an avian coronavirus .^[26] Vitamin C may act as an anti-histamine agent that provide relief from flu-like symptoms like swollen sinuses, sneezing, and running, or stuffy nose .^[27] Three controlled trials with human participants mentioned a significantly lower incidence of pneumonia in vitamin C-supplemented groups, which suggests that vitamin C may affect vulnerability to lower respiratory tract infections .^[28] Recently, a meta-analysis by Ran et al., suggested that extra doses of vitamin C could benefit some patients who contract the common cold despite taking daily vitamin C supplements .^[29] Since, the common cold is a coronavirus like MERS-CoV, SARS-CoV, and COVID-19, supplementation with vitamin C might be beneficial .^[5] The physicians on the Orthomolecular Medicine News Service review board specifically suggested at least 3,000 milligrams (or more) of vitamin C daily by oral, in divided doses^[22] or from 50 to 200 milligrams per kilogram body weight per day to as much as 200 mg/kg/day, intravenously. Furthermore, the results of vitamin C administration intravenously (1 g every 8 h for 3 days) in patients with COVID-19 was reported that vitamin C decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration .^[30] Additionally, findings of bioinformatics analyses suggest that vitamin C administration in COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway, and vascular endothelial growth factor signaling pathway .^[31]

Vitamin D

Vitamin D is an important fat-soluble essential nutrient with a hormone-like activity that exert a beneficial impact on human health .^[32,33] Vitamin D deficiency is one of the most common health problems in the world in all age groups, even in countries with low latitude that UV radiation was enough and in industrialized countries, where vitamin D fortification has been accomplished since many years ago .^[34] Vitamin D stimulates the maturation of many cells including immune cells .^[35] It has been reported that low levels of vitamin D in calves could cause the infection of bovine coronavirus .^[36] Serum levels of vitamin D are affected by seasonal variation, which means a high number of healthy peoples have been reported to be with low levels of vitamin D at the end of the Winter season .^[37] Elderly individuals are more prone to the risk of vitamin D deficiency because of limited exposure to sunlight and a diminished ability of the skin to produce vitamin D .^[38] The COVID-19 was first identified in Winter of 2019 and mostly affected middle-aged to elderly people^[39] who might have insufficient of vitamin D. Besides, a meta-analysis in 2016, had revealed that vitamin D supplementation could be preventive in acute respiratory tract infection especially in people who are very deficient in vitamin D and those receiving daily or weekly supplementation without additional bolus doses .^[40] It has been reported in a single-center, retrospective cohort study that deficient vitamin D status was linked with elevated COVID-19 risk .^[41] On the other hand, the analyses of 502,624 UK biobank participants were identified that vitamin D was associated with COVID-19 infection in crude (odds ratio = 0.99; 95% CI 0.99–0.999; P = .013), but not after adjustment for confounders (odds ratio = 1.00; 95% CI = 0.998–1.01; P = .208) .^[42] A questionnaire-based study among the Italian population reported that vitamin D supplementation could decrease the odds of COVID-19 infection (0.56; 95%CI 0.32–0.99; P = .048) .^[43]

Coronaviruses employed the spike (S) proteins to select and enter target cells. SARS-CoV and COVID-19 S protein engage angiotensin-converting enzyme 2 (ACE2) as their entry receptor .^[44] Augmented expression of ACE2 hastens SARS-CoV infection and spread while the silencing of ACE2 stops its entry into cells .^[45] Organs and tissues with high ACE2 profusion like the kidney, small intestine, and lung are the infection targets of COVID-19 .^[46] ACE2 levels can be increased by the use of renin–angiotensin–aldosterone system (RAAS) inhibitors .^[47] It has been reported that vitamin D could decrease ACE2, reduce ACE expression, reduce angiotensin II production, and downregulate the expression of renin, the rate-limiting enzyme in the renin-angiotensin cascade .^[48,49] These effects are highly relevant to a potential role of vitamin D in protecting against acute respiratory distress syndrome (ARDS) in COVID-19 .^[49]

As a result, it seems that the first step in preventing and reducing the symptoms of coronavirus and especially COVID-19 is to increase the levels of vitamin D up to the normal range. Orthomolecular Medicine News Service review board recommended 5,000 international units (IU) daily for two weeks, and then it should reduce to 2,000 IU/day to prevent or minimize symptoms for future viral infections especially coronavirus .^[22]

Vitamin E

Vitamin E has been known for its oxidative stress diminishing ability through bindings to free radicals as an antioxidant .^[50] Vitamin E deficiency has increased the myocardial injury by coxsackievirus B3 (a kind of RNA viruses) infection .^[51] Furthermore, vitamin E deficiency has increased the virulence of coxsackievirus B3 in mice .^[52] Moreover, vitamin E and D deficient calves were more susceptible to the infection of bovine coronavirus .^[36] Judith et al.^[53] had reported that vitamin E supplementation (200 mg/day) not only showed no favorable effect on the incidence and severity of acute respiratory tract infections in well-nourished elderly individuals but also increases illness severity. Also, vitamin E supplementation with 200 IU/day had no significant effect on the incidence or number of days with an infection for all, upper, or lower respiratory tract infections .^[54] As there is not sufficient evidence regarding vitamin E supplementation, providing RDA amount seems logical in COVID-19 patients.

Minerals

Selenium

Selenium is an essential mineral for mammalian antioxidant defense, redox signaling, and redox homeostasis .^[55] An important parameter for viral replication and pathogenicity is the nutritional status of the host .^[56] It has been demonstrated that the virus could undergo rapid mutation in selenium-deficient host^[57] and selenium deficiency decrease mRNA expression of interferon-γ .^[58] The host selenium deficiency led to oxidative stress and could change the viral genome which may make highly virulent viruses from less pathogenic ones .^[56] Beck et al. had conveyed that selenium deficiency could upsurge the influenza virus pathogenicity and also makes an alteration in the genome of coxsackievirus, facilitating an avirulent virus to acquire virulence due to genetic mutation .^[51,59] Furthermore, it has been revealed that combined treatment of chickens with selenium and ginseng stem-leaf saponins could induce an immune response to a live bivalent IBV .^[60] Additionally, selenium supplementation could promote recovery from acute lower respiratory tract infection caused by a respiratory syncytial virus (RSV) .^[61] Pandemic influenzas type A (H2N2 “Asian,” H3N2 “Hong Kong,” and H5N1 “Avian” influenzas) and SARS-CoV all developed in selenium-deficient areas of China .^[62] When Se-deficient virus-infected hosts were supplemented with dietary Se, viral mutation rates diminished and immunocompetence improved .^[62] The association between the mortality risk of COVID-19 and selenium status was evaluated by Moghaddam et al. .^[63] It has been suggested that the Se status (assessed by serum selenium and selenoprotein P) was significantly higher in samples of COVID-19 survivors as compared with non-survivors (Selenium; 53.3 ± 16.2 vs. 40.8 ± 8.1 µg/L, selenoprotein P; 3.3 ± 1.3 vs. 2.1 ± 0.9 mg/L), recovering with time in survivors while remaining low or even declining in non-survivors. Another document has reported that 42% of COVID-19 patients were selenium deficient. Additionally, a recent report from China has provided evidence regarding the association between hair selenium (as a surrogate data for selenium intake) and COVID-19 which reported that there is a significant correlation between hair selenium and COVID-19 cure rate R² = 0.72, F-test P < .0001 .^[64] Consequently, selenium supplementation might be an effective choice for the prevention and treatment of COVID-19 .^[5] Orthomolecular Medicine News Service review board recommended 100 mcg per day selenium for coronavirus prevention and symptom reduction .^[22]

Zinc

Zinc is another trace element that is crucial for the proper development and maintenance of immune cells in both adaptive and innate immune systems .^[65] Zinc deficiency could increase the susceptibility to infectious disease and its supplementation could converse the effects of zinc deficiency, including impaired immune cell development, compromised T-cell-mediated immune response, and lessened oxidative burst .^[65] A Cochrane systematic review for zinc supplementation in children with measles did not show any significant result for zinc supplementation regarding measles-related morbidity and mortality .^[66] Increasing the concentration of intracellular Zn2+ with zinc-ionophores like pyrithione can effectively impair the replication of a variety of RNA viruses like poliovirus and influenza virus .^[67] Furthermore, zinc and pyrithione combination at low concentrations impedes the replication of SARS-CoV through inhibition of elongation and reduction of template binding .^[67] A proposed dose of zinc supplementation for coronavirus is 20 mg/day based upon Orthomolecular Medicine News Service review board recommendation .^[22]

Other dietary constituents

Probiotics and prebiotics

A probiotic is defined by the WHO as “a live microbial feed that when consumed in adequate amounts confers a health benefit on the host” .^[68] The primary genera of probiotic microorganisms include Lactobacillus (L.) and Bifidobacterium (B.), are found as a part of the gut microbiota and have a long history of being safely used in the form of dairy products .^[69] Prebiotics refer to non-digestible food ingredients that beneficially affect the host microbiome. The best sources of prebiotic foods are grains, legumes, vegetables, chicory, soybeans, and wheat bran .^[70] Several studies have looked into the effects of probiotic or prebiotic consumption on individual immune responses .^[71–73] Probiotics modulate immune and inflammatory response in the gut through their interaction with intestinal epithelial cells and also in the other locations of the mucosal system such as the upper respiratory tract. Increasing evidence suggests that probiotics may also positively induce pro-inflammatory cytokines to facilitate immune response against infection. It has been shown that using probiotics can enhance the host’s resistance against infection .^[69,73] In a randomized, controlled trial in elderly participants, receiving fermented milk containing Lactobacillus, reduced the duration of respiratory and gastrointestinal infections .^[74] Also, dietary intake of the fermented dairy products containing Lactobacillus casei DN-114001 has reduced the duration of respiratory infections in elderly persons .^[75] Makino et al. observed that dietary intake of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augmented natural killer (NK)-cell activity and reduced the risk of common cold and infection in elderly individuals .^[76] Kawashima et al.^[77] showed that Lactobacillus Plantarum (L. Plantarum) strain YU activates helper T lymphocyte (Th1), improves immune responses, and positively influenced viral infection. A meta-analysis by Hao et al. demonstrated that probiotics enhance the immune system and reduce acute upper respiratory tract infections .^[78] It was found that probiotics were more effective than placebo in reducing the episodes of acute upper respiratory tract infection and reducing antibiotic use. According to previous studies, modulating gut microbiota could reduce ventilator-associated pneumonia .^[79] Currently, no clinical evidence proved that modulation of gut microbiota has the therapeutic role in the treatment of COVID-19, but Guidance from China’s National Health Commission recommends that probiotics can be used to maintain the balance of intestinal micro ecology and prevent secondary bacterial infection in severe patients with COVID-19 infection .^[80]

Alpha-lipoic acid

1,2-dithiolane-3-pentanoic acid or alpha-lipoic acid (ALA), is a naturally occurring dithiol compound produced enzymatically in the mitochondrion from octanoic acid. In addition to synthesis, ALA is also absorbed intact from dietary sources including muscle meats, heart, kidney, and liver, and to a lesser degree, fruits, and vegetables .^[81] As an antioxidant, ALA has played a pivotal role as a free radical scavenger to protect against oxidative damage in several diseases including polyneuropathies and hepatic disorders .^[81] Furthermore, the capability to enhance intracellular glutathione (GSH) levels^[82] and normalization of oxidative stress induced by Dexamethasone in chicken had contributed to ALA .^[83] It has been reported that host cells oxidative stress and the glucose-6-phosphate dehydrogenase (G6PD) deficiency were important factors in the infectivity of human coronavirus 229E and treatment of G6PD knockdown cells with ALA could attenuate the elevated susceptibility to human coronavirus 229E infection .^[84] Wu et al. has reported that increased viral infection in G6PD-deficient cells is meliorated by antioxidant agents, such as ALA. Their findings suggest that host redox status is a key factor in viral infection and antioxidants may protect G6PD deficient subjects from viral diseases .^[84] Surprisingly, it has been revealed that ALA was effective to inhibit HIV-1 replication .^[85] Consequently, ALA might be also used as an optional treatment for COVID-19.

Omega-3 polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (PUFA) are imperative mediators of inflammation and adaptive immune responses .^[86] PUFAs are known to modulate the immune system in vivo and to inactivate enveloped viruses in vitro .^[87] Omega-3 and omega-6 PUFAs mainly promote anti-inflammatory and pro-inflammatory upshots and resolvins/protectins and prostaglandins/leukotrienes which are their precursors play these roles .^[88] Begin and colleagues have reported a selective and specific lack of the long-chain PUFAs of omega-3 series in patients with AIDS, which are found in high concentrations in fish oils .^[87] Protectin D1 (PD1) is a PUFA-derived lipid mediator which markedly attenuated influenza virus replication via RNA export machinery. During severe influenza, PD1 production was suppressed and its levels inversely correlated with the H5N1 viruses’ pathogenicity. Furthermore, treatment with PD1 in mice with severe influenza rescue from flu mortality .^[89] Leu et al. had documented that several PUFAs also had an anti-hepatitis C virus (HCV) properties .^[90] Therefore, Omega-3 fatty acids might be considered for one of the potential interventions of this novel virus, COVID-19.

Flavonoids

Flavonoids are plant-derived natural products with human health-promoting benefits which consisted of several subgroups including flavonols, isoflavones, flavones, and chalcones .^[91] Besides antioxidant properties, they also have antiviral abilities. It had shown by Shimizu et al. that flavonoids from Pterogyne nitens inhibit hepatitis C virus entry but exert no inhibitory effects on HCV replication and release .^[92] Furthermore, herbacetin, rhoifolin, and pectolinarin were found to efficiently block the SARS-CoV and herbacetin, isobavachalcone, quercetin 3‐β‐d‐glucoside, and helichrysetin the MERS‐CoV enzymatic activity of 3 C-like protease (3 CLpro) .^[93,94] Additionally, it has been proved by Ryu et al. that biflavonoids from Torreya Nucifera could exert an inhibitory effect on 3CLpro of SARS-CoV .^[95] Consequently, Flavonoids should be kept in mind as a potential therapy for COVID-19.

Herbal medicine

Viral infections are responsible for several human diseases and many viral infections are still causing a tremendous threat to humanity, particularly when anti-viral drugs and preventive vaccines are unavailable. Consequently, alternative herbal medicines are an urgent need to discover highly efficacious novel antivirals that are for the management and control of viral infections. Several herb and natural therapies have been used widely for the prevention and treatment of respiratory viral infections .^[96,97]

Curcumin

Curcumin [1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione], is a major phenolic compound of the plant Curcuma longa rhizome, and exert various functions, including antioxidant, anticancer, anti-inflammatory, and antiviral effects .^[98–101] Curcumin as a modulator of inflammatory signaling pathways in the immune system effectively disrupted the NF-kB pathway and reduced expression of pro-inflammatory cytokines which could be used against virus-induced cytokine storm and associated severe pneumonia. Besides, curcumin inhibited NF-κB via the activation of AMPK .^[102] Obata et al. has reported that curcumin can avert the RSV replication and the epithelial responses to RSV without cytotoxicity and may be useful for severe lower respiratory tract disease treatment in infants and young children .^[103] Several investigations examined the effect of curcumin on different influenza A virus (IAV) types through in vitro studies and found it to impede virus uptake, replication, and particle production .^[104–106] Moreover, direct antiviral activity, recent in vivo attempts revealed that curcumin treatment lessens lung inflammation due to IAV infection in mice and upsurge the immune response against IAV in turkeys .^[106,107] Recently, Chen et al. reported that a combination of vitamin C, curcumin, and glycyrrhizic acid (VCG Plus) has potential against COVID-19 .^[108] VCG Plus has the potential to regulate innate immune and inflammatory responses. VCG Plus could be considered for potential interventions for COVID-19 infection; however, further in vitro and in vivo experiments are needed.

Ginger

The rhizome of Zingiber officinale, ginger, is a member of the Zingiberaceae family that has been used as a spice globally. It has been revealed by Pius et al., that 17 bacteria species associated with respiratory tract infection (RTI) are susceptible to aqueous and the methanol extracts of ginger .^[109] Another in vitro study by Chang et al. has proposed that fresh, but not dried, ginger is efficient against human RSV-induced plaque formation on airway epithelium by blocking viral internalization and attachment .^[110]

Echinacea

Echinacea purpurea, the purple coneflower, was commonly used by Native peoples and later by the Eclectic practitioners of North America long before the presentation of European medicines, principally as treatments for various infectious diseases and wounds .^[111] The alkamides are the main constituent of echinacea that stimulate the immune system and may have crucial modulatory effects on macrophages and NK cells .^[112] A meta-analysis reported that Echinacea significantly decreased the incidence of the common cold by 58% and the duration of a cold by 1 · 4 days .^[113] Another meta-analysis by Schapowal et al. documented that Echinacea effectively lowers the risk of recurrent respiratory infections and associated complications .^[114] In a study by Engler and colleagues, Echinacea revealed a dose-dependent reduction of Coronavirus 229E and MERS-CoV activity .^[115] In agreement with previous studies, Coronavirus 229E, MERS-CoV, and SARS-CoV were inactivated by Echinacea in vitro study .^[116]

Garlic

Garlic (Allium sativum) has been used traditionally for both culinary and medicinal purposes .^[117] A wide range of pathogenic organisms, including protozoa, bacteria, fungi, and viruses be delicate to fresh garlic .^[118] Garlic extract has shown an inhibitory effect on IAV penetration and proliferation in cell culture .^[118] Shojai et al. conclude that the Allium sativum had inhibitory effects on the infectious bronchitis virus (IBV), a disease caused by a coronavirus, in the chicken’s embryo. It seems that Allium sativum can be an appropriate herbal extract for other coronaviruses diseases .^[119] A Cochrane systematic review concluded that garlic may prevent common cold incidence, but more studies are needed to validate the effectiveness of garlic in preventing or treating the common cold .^[117]

Green tea

Green tea, a popular drink in Asian countries, has a variety of health benefits including antioxidant, anti-inflammatory, anti-carcinogenic, and antimicrobial effects. Green tea has been shown to have antimicrobial effects against a variety of viruses (e.g., HIV, herpes simplex virus (HSV), and influenza) .^[120] epigallocatechin-3-gallate (EGCG) is active polyphenolic catechin and the main constituent of green tea .^[121] For most of the enveloped viruses, like HCV, HIV, HSV, and influenza, ECGC has been shown to alter or damage the virus particles and so prevent viral entry .^[120,121] Several animal studies are shown green tea extract or EGCG could inhibit neutrophil recruitment to the inflammation sites and inhibit neutrophil proteolytic enzymes .^[69,122,123] COVID-19 is related to hyper inflammation conditions. The oral administration of EGCG inhibits monocyte migration by reducing the secretion of the chemokine monocyte chemotactic protein-1 (MCP-1) and its receptor expression as a prominent proinflammatory mediators .^[124] In addition, EGCG could inhibit the activation of NF-kB and as a result controls the expression of pro-inflammatory cytokines .^[125] The mechanisms for EGCG-induced inhibition of T cell proliferation are yet to be clearly understood; however, some in vitro studies suggests EGCG inhibits the early stages of the T cell signaling pathways .^[126] EGCG appears to have a potential benefit in clinical application for prevention and mitigation of T cell-mediated autoimmune diseases by anti-inflammatory, T cell suppressing, and differentiation-modulating effects on T cell subset development .^[69,120,121] Since all the available documents were from animal studies, further investigation through human clinical studies are needed,

Ginseng

One of the most common medicinal plants used in traditional medicine in East Asian is Korean ginseng. Ginseng contains ginsenosides as major bioactive compounds, polyacetylenes, phytosterols, polysaccharides, and essential oils .^[127,128] Ginsenosides protects human endothelial cells against influenza H9N2-induced inflammation and apoptosis .^[129,130] Lee et al. has reported that the Panax Korean red ginseng extract (KRGE) could exert antiviral activity against RSV infection via decreasing lung viral loads and enhancing the level of interferon-γ .^[130] Panax notoginseng root (PNR), also known as Sanchi, is used as an herbal medicine in Korea and China. PNR has been used to treat non-communicable diseases due to its antihypertensive, antioxidant, anti-inflammatory, anticoagulation, antiatherosclerotic and antimicrobial effects .^[131] Also, PNR could prevent influenza virus infection, viral protein, and mRNA expression. PNR treatment decreased mortality by 90% and enhanced NK cells in mice exposed to the virus .^[132,133] NK and inflammatory cytokines in influenza A H1N1 are the first line of defense against viral infection and virus replication .^[131–133] It has been reported that PNR can stimulate NK cell activity and inhibit influenza virus infection in vitro and in vivo .^[132] PNR has stimulated an antiviral response of macrophages, inhibited the expression of viral protein and mRNA in infected mice. Furthermore, in mice exposed to the influenza A H1N1 virus, PNR prevented weight loss and reduced viral infection .^{[114,132,134]} Consequently, ginseng revealed promising protective properties against viral infection.

Cinnamon

For thousands of years, cinnamon has been used as a health-promoting agent for the treatment of inflammation, gastrointestinal disorders, urinary tract infections, diarrhea, flatulence, and infectious disease. The main bioactive compounds of cinnamon are polyphenols and volatile phenols .^[135,136] Hayashi et al. showed that trans-cinnamaldehyde of cinnamon could inhibit in vitro and in vivo influenza A/PR/8 virus propagation .^[137] Fatima et al. has reported that the silver nanoparticles derived from cinnamon extract had potent antiviral activity against avian influenza virus subtype H7N3. They tested for cinnamon cytotoxic effects in Vero cells and revealed concentrations of extract and nanoparticles (up to 500 µg/ml) were nontoxic. The mechanism of the antiviral action of cinnamon needs to be further investigated .^[138]

Conclusion

In the current review, we summarize all the potential nutritional interventions for COVID-19 infection according to previous treatments of SARS-CoV, MERS-CoV, and recent findings of COVID-19. It has been found that the general treatments are crucial to improve host immune response against RNA viral infection. The immune response has often been revealed to be debilitated by nutritional deficiencies in many pre-clinical and clinical studies. Against this background the following conclusions are made:^[1] supplementation with the above micronutrients, omega-3 fatty acids, and probiotics is a safe, effective, and low-cost strategy to help support optimal immune function;^[2] supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C, D, and selenium is warranted; and^[3] public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

Acknowledgement

All authors contributed equally to the writing and revision of the manuscript. The authors declare no conflict of interest. The authors would like to thank Dr. Parisa Mirmoghtadaei.

Additional information

Funding

This research received no external funding.