Viruses are particles that exploit the RNA and DNA of other cellular life forms in order to proliferate and survive. The introduction of viruses to a host promotes viral propagation by altering the host’s normal genomic and metabolic state. (67)(115)
Viral invasion can lead to a variety of outcomes, ranging in severity. An infection may be acute, mild, and quickly resolved by the host’s immune system (e.g., the common cold), or the infection may be severe, even fatal, and lead to chronic disease. Commonly recognized viruses may include, but are not limited to, the following:
Unlike bacteria, fungi, and eukaryotic parasites, which are living cells that use their own cellular DNA for replication, viruses are not living cells and require the genetic information present in host cells in order to replicate. Viruses are characterized by an outer protein shell, known as a capsid, which houses limited amounts of genetic material (RNA or DNA). The entirety of the genetic information and the outer protein shell is referred to as a virion. In order to replicate, the genetic information contained within the virion must be transmitted into a host cell. (5)
The outer surface of the virus possesses proteins recognized by specific cellular receptors on host cells, which initiates virus transmission. The virus’ genetic material can then penetrate the cellular nucleus to interact with the host’s DNA to produce mRNA, which ultimately leads to viral proteins that may generally be classified by three functional characteristics:
The accumulation of virions in the host cell may eventually lead to cellular death as the infected cell either ruptures or disintegrates. Transmission then occurs by diffusion within extracellular space, transfer through temporary cellular membranes from non-lysed cells or other migratory cells, or by the carriage of the virus to non-infected cells through surface-to-surface contact. (77)(107)
Viral invasion can lead to a variety of symptoms, ranging in severity.
While viral infections are often characterized by their pathogenic actions (e.g., respiratory viruses, gastrointestinal viruses, neurological viruses, etc.), viruses are more accurately classified by their characteristic RNA or DNA, as well as the mode by which they approach replication and expression. The seven classes of viruses are labelled as:
RNA viruses contain RNA as their genetic material, while DNA viruses have DNA. The mechanisms of infection of RNA and DNA viruses typically produce acute and chronic viral infections, respectively. (28) Single strand RNA viruses such as (+)strand RNA viruses can match host mRNA and can be immediately translated into viral proteins, while (-)strand RNA complement viral mRNA but require conversion to (+)strand RNA before translation into viral proteins. (28)(67)
After a viral invasion, your body’s innate and adaptive immune systems respond to the virus’ presence. A variety of cellular receptors are used to recognize when a pathogen has invaded or created byproducts that are potentially harmful to the body. This ultimately leads to the upregulation of immune, pro-inflammatory, and other products that attempt to remove or interfere with viral replication. (11)
Prevention of viruses mainly focuses on providing the body with a means of recognizing the pathogenic virus so that the immune system can ultimately react in a manner to disrupt viral spread. Vaccines are introduced into the body as a ‘practice run’ so that cellular receptors can effectively recognize and react to the presence of the viruses by inducing the immune system. (11)
Unlike bacterial pathogens, viruses cannot be killed by anti-microbials, and anti-biotics are often incorrectly prescribed to address viral infection. (96) Most viral infections do not require specific anti-viral drugs and are resolved by the body’s immune system. However, some anti-viral treatments may provide supportive functions by reducing the severity of symptoms or by suppressing viral recurrence. (12)(103)
Viral transmission may depend on the relationship between the characteristics of potential hosts, a host’s environment, and the pathogen itself. Pathogens may spread to new locations as a result of travel, migration, or trade, particularly with the global ability of rapid air travel and increasing population density.
Furthermore, approximately 80% of human viral infections proliferate in animals and arthropods, which increases the risk of transmission following contact with vulnerable human populations. (94)
Viral susceptibility also varies based on the pathogen itself, as well as the characteristics of the host. Differences in health, nutritional and immune statuses, genetics, physiology, and age, as well as the presence of previous or simultaneous viral infections are all contributing factors. (94)
Practicing good hygiene is an effective way to reduce viral transmission.
Practicing good hygiene is an effective way to reduce viral transmission.
Maintaining a healthy and balanced diet is intricately connected to proper immune function. (21) There are several food sources that contain anti-oxidant and anti-viral properties that may assist in providing immune system support.
Anti-oxidants prevent or reduce oxidative stress that is associated with most chronic diseases. Anti-oxidants can contribute to cellular maintenance, DNA repair, and longevity. Foods with the highest anti-oxidant profiles include berries, fruits, nuts, chocolate, and vegetables. Plant-based foods including spices and herbs also contain high proportions of anti-oxidants. (14)
Incorporation of herbs and spices into the diet is another way to ingest foods that have demonstrated anti-viral properties. Namely, immune supportive herbs or their active components, which can be found in other natural products such as supplements, and may specifically target viruses of the Coronavideae family include:
The following provides a list of supplements that have been used as immune system support for viral infections.
The roots of Astragalus membranaceus have been used therapeutically for thousands of years in Traditional Chinese Medicine for its bioactive polysaccharides. As demonstrated in various studies, these polysaccharides possess widespread immunomodulatory, anti-inflammatory, anti-viral, anti-oxidant, and cardioprotective activities. (133)
In humans, Astragalus membranaceus formulations as injection or granules have been used as supportive therapy for myocarditis induced by viral infections. (42)(76) Oral liquid administrations have been shown to enhance cellular immunity in viral myocarditis patients. Specifically, OKT3, OKT4 cells and the OKT4/OKT8 ratio increase. (54) The use of 7.5 ml twice per day (equivalent to 1.23g of dry herb) for one week has also been shown to stimulate CD69 expression on white blood CD4 and CD8 T cells within 24 hours, which is maintained during the week of ingestion. (13) In comparison, stimulation of CD25 expression was greatest in the first day but not maintained over the rest of the week. (134)
Astragalus treatment can boost ɑ-interferon (ɑ-IFN) and γ-interferon (γ-IFN), cytokines which play roles in viral replication. (124) Its anti-viral properties have also been demonstrated in patients with chronic viral hepatitis B by promoting recovery from viral infection and by preventing viral replication (81)(114). Astragalus extracts can also reduce the level of anti-inflammatory IL-4 and IL-10 cytokines, while increasing pro-inflammatory IL-2 and immune response-inducing γ-IFN in patients with viral herpes simplex keratitis. IL-4 and IL-10 may be typically reduced, while IL-2 and γ-IFN may be typically higher in these patients. (80)
Astragalus membranaceus has also been shown to possess anti-influenza virus properties by modulating the expression of toll-like receptors (TLR) TLR3, transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), TRAF-family member associated NF-κB-activator (TANK) binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and interferon-β (IFN-β) in the TLR3-mediated signaling pathway in vitro. (74) TLR-mediated pathways are involved in the activation of various inflammatory responses with exposure to pathogens. (93) Furthermore, it provided anti-oxidative effects by increasing superoxide dismutase and reducing MDA. (74)
Echinacea (Echinacea purpurea) is a medicinal herb widely used for its immune-boosting properties. For common cold prevention, the use of a liquid extract, 0.9 ml three times per day (equivalent to 2400 mg of extract) for a minimum of four months has been used, while in the acute phase of cold development, up to 4.5 ml (4000 mg) has been used. (56) Meta-analysis shows that echinacea use may reduce the risk of common cold development by 10-58%, and days with cold by approximately a day and a half. (59)(108) Echinacea may reduce the incidence of cumulative viral infections by 26% and recurring infections by 59%, including the influenza virus and parainfluenza virus. (56) Its immune-boosting effects may be related to associated increases in immune cell counts including white blood cells, monocytes, neutrophils, and natural killer cells, which fight infection. Furthermore it may increase the suppression free radical production production in the later-phase of the cold by neutrophils. (38) Free radicals such as superoxide may have a role in the pathogenesis of viral infections. (4)
Black elderberry (Sambucus nigra) contains various bioactive constituents such as anthocyanins, which have been shown to have anti-viral and immune-stimulating properties. A 2019 meta-analysis showed that elderberry supplementation substantially reduced the symptoms of viral URTIs, particularly for the influenza virus. (44)
Black elderberry has been shown to have anti-viral and immune-stimulating properties.
Dosing and administration protocols have varied between published trials, but consistently improve symptoms of cold and flu, and reduce duration of infection. Two trials have shown efficacy with the administration of 15 ml (1 tablespoon) of an elderberry standardized extract syrup, four times per day to adults during meals for three to five days while children use half doses. (126)(127) Another study used slow-dissolving lozenges containing 175 mg of a proprietary elderberry extract, four times per day with meals and before bed, over two days. (66) Finally, proprietary extract capsules containing 300 mg of elderberry extract has been provided as two capsules per day for ten days prior to air-travel, and three capsules for four to five days at the destination have been used. (117)
Goldenseal (Hydrastis canadensis) has been traditionally used as an anti-infectious ingredient, and now used in supplements for colds and respiratory tract infections, however, there is a current lack of human clinical trials using the whole plant or an extract. (88)
Goldenseal has been shown to inhibit the growth of influenza A and inflammatory markers in vitro. (17) It has also demonstrated anti-microbial activity against methicillin-resistant Staphylococcus aureus and Helicobacter pylori in vitro, which are two pathogenic bacteria responsible for the development of a variety of health conditions. (16)(23) Goldenseal may also modulate the anti-inflammatory and pro-inflammatory response as it may reduce the production of inflammatory biomarkers such as TNF-ɑ, interleukin IL-6, IL-10, and IL-12 from macrophages. (20) In rats, goldenseal also increased immunoglobulin M (IgM) response within two weeks of use. (104) IgM is produced in response to antigens and may protect against viral infections including influenza. (9)
One of the constituents of goldenseal, berberine, has also demonstrated anti-viral properties. In the lung cells of mice, berberine inhibited influenza virus replication and reduced the virus-induced alteration of immune cell ratios and rises in inflammatory markers. (123) It has also shown anti-viral activity in vitro to many other viruses by preventing viral entry and replication. Examples include Coxsackievirus B, Cytomegalovirus, Enterovirus, respiratory syncytial virus Hepatitis C, Zika viruses, to name a few. (8)(24)(55)(110)(121)(132)
The essential amino acid L-lysine has been used in a wide variety of applications. In relation to anti-viral therapy, L-lysine has been most studied for its uses in herpes simplex virus infections. (113) Many trials have used doses ranging between 300-3000 mg per day for up to one year for herpes prophylaxis and symptom treatment. (41)(82)(85)(111)(116) However, systematic reviews indicate that treatment with more than 1 gram may be required for prophylaxis or treatment of the herpes viruses, while doses greater than 3 grams per day can improve patient’s self-assessed improvements. (78)
A trial supplying 1000 mg of lysine per day for 16 weeks to a population where bacterial and viral causes of diarrhea commonly occur also showed a reduction in diarrhea episodes and days of sickness in children, while reducing the number of days with sickness and number of episodes of coryza in men. In women, serum ferritin and CRP levels decreased with lysine supplementation. (36) These biomarkers may be increased in the presence of influenza infections. (33)
Intake of shiitake mushrooms has been shown to stimulate the immune response.
Similarly to astragalus, mushrooms and their active components have been extensively used in Traditional Chinese Medicine for their immune-stimulating, anti-microbial, anti-fungal, anti-tumor, and anti-viral properties. (131)
Several in vitro studies have shown broad anti-viral effects, including anti-viral effects against influenza, using a variety of mushroom extracts including Ganoderma lucidum, Lentinus edodes, Grifola frondosa, Agaricus brasiliensis, (6)(32) Phellinus igniarius, (69) and Rozites caperata. (97) The following provides evidence for the use of medicinal mushrooms and their bioactive ingredients in viral infections from human trials.
The ingestion of lentinan, a major active substance in Lentinus edodes mushrooms at doses of 2.5 mg per day for six weeks also increased the number of circulating B lymphocytes in healthy elderly adults. (34) As an adjunct anti-viral therapy in patients with HIV, 2 mg (i.v.) of lentinan increased the CD4 cells for up to 38 weeks compared with anti-retroviral therapy alone. (40)
Another extract from Basidiomycetes mushrooms called the ‘active hexose correlated compound’ has been used to improve immune status of healthy individuals after receiving the influenza B vaccination. Ingesting 3 grams per day for three weeks post-vaccination increased the number of natural killer cells and CD8 T cells, and improved antibody titers to influenza B compared with vaccine alone. (105)
The daily use of 1.5 grams of Agaricus blazei Murill has been safely used over one year to reduce aspartate and alanine aminotransferases in patients with hepatitis B. This may provide indication that Agaricus blazei Murill may assist in the normalization of liver function following its infection by the hepatitis virus. (52)
In healthy adults, the use of 5 to 10 grams of Shiitake mushrooms over four weeks has been shown to stimulate γδ-T cells, natural killer T cells, and secretory IgA, involved in the immune response. Consumption may alter the inflammatory profile as shown by reduced C-reactive protein (CRP), and macrophage inflammatory protein-1α/chemokine C-C ligand 3 (MIP-1α/CCL3) levels, and increased IL-4, IL-10, TNF-α, and IL-1α levels. (25)
Another medicinal mushroom product called Immune Assist 25/7™ containing compounds Lentinus edodes, Trametes versicolor, Ganoderma lucidum, Agaricus brasiliensis, Cordyceps sinensis, and Grifola frondosa at a dose of 2.4 g for two months increased CD4+ T-lymphocyte numbers in HIV patients. (1) The combination of Trametes versicolor and Ganoderma lucidum has been shown to clear oral human papillomavirus 16 and 18 after two months of treatment. (29)
The herb, oregano (Origanum vulgare) is commonly used in the food, cosmetics, and pharmaceutical industries. The essential oils are now also used for their anti-microbial, anti-viral, and anti-fungal properties. (73)
Oregano essential oils are used for their anti-microbial, anti-viral, and anti-fungal properties.
Studies have assessed the anti-viral activity against certain viruses, including the murine norovirus, respiratory syncytial virus (RSV), Coxsackie virus B3 (CVB3), and herpes simplex virus type 1 in vitro. (37)(129)
Though probiotics have been most widely used for their beneficial effects in the GI tract, research now shows that a healthy composition of bacteria in the GI tract can translate to improved immune function. This can also lead to improved regulation of anti-inflammatory and pro-inflammatory cytokines, and anti-oxidative biomarkers. (7)(83)(106)(128)
The benefits of probiotics can extend beyond their anti-microbial effects to also provide support against viral infections. For example, research is showing the potential benefit of probiotics as an adjunct therapy for in the regulation of white blood CD4 cell counts in patients with human immunodeficiency virus (HIV). (15)(22)(60)(84)(122)
Meta-analyses show that probiotics may reduce cold severity and have minor effects on cold prevention, as well as improve influenza vaccination efficacy for A/H1N1, A/H3N2, and B strains, but is dependent on strain and population. (58)(71)(125) Meta-analyses also show the efficacy of probiotics in reducing rates of respiratory tract infections in adults and children. (27)(43)(64)(92)(120)
In children, the use of 5 billion CFU of Lactobacillus acidophilus NCFM (ATCC 700396), twice per day, for a minimum of six months has been shown to reduce the incidence and severity of cold symptoms, while 10 billion CFU of Bifidobacterium animalis subs. lactis Bi-07 (ATCC PTA-4802) and Lactobacillus acidophilus NCFM (ATCC 700396), had similar effects for influenza. (72)
In adults, the use of 1 billion CFU of Lactobacillus paracasei 8700:2 (DSM 13434) and Lactobacillus plantarum HEAL 9 (DSM 15312), once per day for three months can reduce the incidence of colds and symptoms. (10) For influenza, 10 billion CFU of Lactobacillus fermentum CECT5716, once per day for two weeks before influenza vaccination and two weeks after, or Lactobacillus rhamnosus GG, twice per day for four weeks after influenza vaccination may reduce the future incidence of influenza compared with vaccination alone by increasing seroprotection (the extent of increased antibodies in response to infection), as well as natural killer cells, the T-helper response, and immunoglobulin A levels. (26)(91) The use of another probiotic, Saccharomyces cerevisiae (EpiCor®) at a dose of 500 mg per day for 12 weeks may reduce the incidence of cold/flu symptoms with or without prior vaccination and the duration of symptoms with prior vaccination. (86)(87)
Quercetin, a flavonoid found in many plant-based foods, has also shown efficacy in reducing the incidence and severity of upper respiratory tract infection (URTI) symptoms. A dose of 1000 mg per day has been shown to reduce the severity of URTI symptoms as well as the number of sick days, particularly for adults over the age of 40. (45) The same dose over two weeks also reduced the incidence of URTIs in trained athletes. (89)
A derivative molecule of quercetin, quercetin 3-β-O-d-glucoside has been shown to provide protection against ebola viruses in mice and in vitro. (101) Several other studies in vitro studies have demonstrated anti-viral properties against Influenza, Mayaro, Chikungunya, Epstein-Barr, and Hepatitis C viruses. (30)(61)(63)(68)(70)
Vitamin C is one of the most popular immune support vitamins when it comes to the common cold and flu. Systematic reviews and meta-analyses indicate that supplementation with a minimum of 200 mg in children and 1 g of vitamin C per day in adults may be used as an ongoing maintenance dose to boost immunity. Increasing the dose to 1 to 2 g in children and 3 to 4 g in adults at the onset of common cold symptoms can reduce the duration of infection. This may be a result of increased anti-microbial, and immune cell activities, as well as improved anti-oxidant capacity. (48)(102)
Vitamin D has been shown to be involved in modulation of the immune system due to its ability to bind to vitamin D receptors expressed throughout the body’s nucleated cells, including antigen-presenting cells within the innate and adaptive immune systems. (18) Vitamin D insufficiencies or deficiencies have been linked to a variety of viral infections, including chronic hepatitis B, (53) hepatitis C virus, (119) or other viral infections leading to upper respiratory tract infections or pneumonia. (2)(98)
Vitamin D may also be used in the prevention and/or treatment of URTI in adults and children. One meta-analysis showed that doses ranging from 400 to 2000 IU per day over three months to three years reduced the incidence and number of events of respiratory tract infections in children and adults. (19) A four-month protocol of 400 IU of daily vitamin D also reduced the duration and severity of URTIs in adults. (109) In children aged one to five, daily administration of 400 IU for four months was equally as effective as 2000 IU in reducing the risk for wintertime URTIs, (2) though doses of 1200 IU for approximately four months in the winter can reduce the incidence of Influenza A in children aged six to 15, (118) and in infants of less than one year of age. (130) In older Vietnamese children aged three to 17, weekly ingestion of 14000 IU over eight months reduced the incidence of non-influenza respiratory virus infections, but not influenza infections. (78)
Vitamin D administration as an adjunct to other anti-viral therapies may have synergistic benefits in infections such as chronic hepatitis C (62) and HIV, (31) and may reduce inflammatory markers, such as TNF-α and IL-6, after influenza vaccination, while promoting transforming growth factor beta (TGF-β), a multifunctional cytokine involved in cell growth, proliferation, and programmed cellular death. (39)
Zinc is also often recommended for its protective effect against the common cold. Zinc improves the anti-inflammatory and anti-oxidant profile by reducing in plasma interleukin-1 receptor antagonist, intercellular adhesion molecule-1, TNF-ɑ, malondialdehyde (MDA), 4-hydroxyalkenals (HAE), and 8-hydroxydeoxyguanine (8-oHdG), and increases in IL-2 mRNA in mononuclear cells. (99)(100) The symptoms of viral infections, including those of the common cold, are considered to be consequences of the increased presence of pro-inflammatory cytokines such as TNF-ɑ and many interleukins in response to viral invasion. (65) MDA, HAE and 8-oHdG are examples of biomarkers that lead to the production of free radicals, (35) which, as previously described, may have roles in the pathogenesis of viral infections. (4)
Several systematic reviews and meta-analyses show that 75 to 100 mg of elemental zinc as zinc acetate or zinc gluconate lozenges, once per day, within 24 hours of the onset of common cold symptoms, minimum 1 to 2 weeks to reduce the duration and symptoms of colds, in adults and children. (46)(47)(49)(50)(57)(112)
Viruses are particles that require a host in order to proliferate and survive. Viral infections may be asymptomatic, but can lead to mild symptoms and conditions, or more severe and chronic conditions, including death.
Practicing good hygiene can effectively reduce the risk of viral spread and infection, but maintaining a strong immune system to ensure appropriate immune responses to viral infections occur is critical. There are several best practices that can be used to support immune function, including several immune-boosting foods and supplements that may be used for their anti-viral properties.