Table 1.

Micronutrients and bioactive substances with immunomodulating, antiinflammatory, antioxidant, and antiviral properties

Micronutrients and bioactive substances	Targets	Specific effects	Reference
Vitamin A	Immune response	Maintains integrity of respiratory epithelium	[33,41]
		Has protective effects in many respiratory pathologies	[42]
		Regulates the expression of retinoic acid-inducible gene I and interferon-regulatory factor 1	[46]
Riboflavin	Antiviral property	Together with ultraviolet light effectively reduced Middle-East respiratory syndrome coronavirus titer	[55]
Nicotinamide	Immune response	Inhibits neutrophil infiltration	[56]
Pyridoxine	Immune response	Improves immune responses	[57]
Folate	Immune response	Plays crucial role in DNA and protein synthesis in cells	[58]
Vitamin B12	Immune response	Improves high CD4/CD8 ratio and suppresses natural killer cells	[59]
Vitamin C	Antioxidant	Protects against reactive oxygen species	[65]
		Inhibits the production of cytokines storm	[28]
	Immune response	Highly concentrated in phagocytes and lymphocytes, suggesting a physiological role in immune cells	[60]
		Supports epithelial barrier function against pathogens	[62]
		Improves immune system activities	[65]
		Increases production of interferon-α/β	[68]
	Antiviral property	Dehydroascorbic acid showed strong antiviral activity	[69]
Vitamin D	Antiinflammatory	Downregulates proinflammatory cytokines (cytokine storm)	[23,78]
		Increases expression of antiinflammatory cytokines	[83]
		Stimulates T reg cells development	[84]
		Enhances expression of glutathione reductase and glutamate–cysteine ligase	[79,80]
	Immune response	Stimulates maturation of immune cells	[9]
		Attenuates lipopolysaccharide-induced acute lung injury by, at least partially, inducing ACE2/Ang 1-7 axis activity and inhibiting renin and the ACE/Ang II/Ang II type 1 receptor cascade	[31]
	Antiviral property	Explained by inducing the release of cathelicidin LL-37 and human b defensin 2	[76]
Vitamin E	Antioxidant	Reduces oxidative stress through binding to free radicals	[93]
Zinc	Replication cycle	Interferes with 3 chymotrypsin-like protease	[106], [107], [108], [109]
	Antiinflammatory	Inhibits the expression of proinflammatory cytokines, chemokines, acute phase proteins (C-reactive protein and fibrogen) through inhibiting nuclear factor κB signaling	[113,116,117]
		Modulation of regulatory T – cell functions that may limit the cytokine storm in coronavirus disease 2019	[118]
	Immune response	Involves in maintenance and development of innate and adaptive immune system	[119]
		Considered as second messenger of immune cells	[113]
	Antiviral property	In combination with pyrithione at low concentration inhibits the replication of severe acute respiratory syndrome coronavirus	[109]
Selenium	Antioxidant	Antioxidant properties of amino acid selenocysteine	[100]
		Inhibits inflammatory process (cell injury) through Se-dependent glutathione peroxidase	[99]
	Immune response	Induces immune response	[101]
	Antiviral property	Diminishes viral mutation and improves the immunocompetence of patients with selenium deficiency	[100]
Anthraquinone emodin	Entry site	Interferes with attachment and fusion of spike protein and ACE2 receptor	[126]
Curcumin	Entry site	Interferes with attachment and fusion of spike protein and ACE2 receptor	[125]
	Antiviral property	Reduces infectivity of virus in dose–time dependent manner	[125]
Echinacea purpurea	Antiinflammatory	Suppresses proinflammatory responses	[150]
	Antiviral property	Has effect on virus during initial infection and at time of transmission	[150]
Garlic	Replication cycle	Interferes with RNA-dependent RNA polymerase	[148]
	Antiviral property	Has antiviral activities	[146,147]
		Used in management of common cold	[122]
Ginseng	Immune response	Has immunomodulatory effects	[122,158,159]
Green tea (containing EGCG, ECG, and EGC)	Entry site	Inhibits transmembrane protease serine 2	[134]
	Antiviral property	Possesses broad range of antiviral spectrum	[135,136]
		Has antiviral effect on influenza virus by altering physical properties of viral membrane	[137]
Nicotianamine	Entry site	Interferes with attachment and fusion of S-protein and ACE2 receptor	[127]
Propolis	Antiinflammatory	Antiinflammatory activity	[151,154,155]
	Antiviral property	Has antiviral activities	[154]
Quercetin	Entry site	Reduces endocytosis	[142]
	Replication cycle	Interferes with 3 chymotrypsin-like protease	[9,[143], [144], [145]
	Antiviral property	Has antiviral activities	[140]
Resveratrol	Antiviral property	Has antiviral activities	[157]
Sulforaphane	Entry site	Inhibits transmembrane protease serine 2	[33,128,129]
	Antioxidants	Decreases oxidative stress and inflammation	[132]

ACE, angiotensin converting enzyme; Ang, angiotensin; CD, cluster of differentiation.