The 2019 novel coronavirus, SARS-CoV-2, producing the disease COVID-19 is a pathogenic virus that targets mostly the human respiratory system and also other organs. This virus is a great threat to public health and global economies. The novel coronavirus, SARS-CoV-2, causes severe acute respiratory syndrome and has quickly become a serious threat to public health. Since the initial cases were reported in Wuhan, China, the virus has quickly spread globally, affecting more than 200 countries.
The primary mode of human to human transmission of SARS-CoV-2 has been identified to be through respiratory droplets. COVID-19 symptoms appear after an incubation period of around 2–14 days. The duration from the onset of symptoms to death has ranged from 6 to 41 days. However, this duration is dependent on both the age of the patient and the status of their immune system. Patients over 70 years of age seem to be more susceptible to this virus, probably as a result of a weaker immune system. SARS-CoV-2 infection has been associated with many symptoms and clinical signs. However, based on hospitalised data, patients mainly exhibited symptoms of acute respiratory distress syndrome, associated with pyrexia, cough, fever and fatigue. Additionally, one study found that approximately 80% of patients reported being asymptomatic or with mild symptoms. The remaining 20% of cases, however, were more critical and severe.
Currently, no specific treatment for COVID-19 has been recognised; however, certain drugs have shown apparent efficacy in viral inhibition of the disease. Natural substances such as herbs and mushrooms have previously demonstrated both great antiviral and anti-inflammatory activity. In this review, we have evaluated the most effective herbs and mushrooms, in terms of the antiviral and anti-inflammatory effects which have been assessed in laboratory conditions.
There are many populations that prefer the use of natural products in place of commercial pharmaceutically developed products for treating and preventing medical illnesses. Many cultures around the world have historically relied on medicinal plants for primary care, with some continuing use till this date. It is widely known that herbs are used as part of natural medicines primarily in Asian countries such as China. Herbal plants and purified natural products provide a rich supply for the development of novel antiviral compounds.
Prunella is a genus of perennial herbaceous plants in the Labiatae family. Approximately 15 species have been identified worldwide, most of which are distributed in the temperate regions of Europe and Asia. From this genus, the most extensively studied is Prunella vulgaris (selfheal) due to its several thousand-year histories as an antipyretic and antidotal herb used in traditional Chinese medicine. The Prunella genus is known to contain triterpenoids and their saponins, phenolic acids, sterols and associated glycosides, flavonoids, organic acids, volatile oil and saccharides. Various pharmacological studies investigating Prunella have demonstrated the enhanced antiviral, antibacterial, anti-inflammatory, immunoregulatory, anti-oxidative and anti-tumour properties it possesses. Prunella vulgaris is a herbaceous plant that is commonly known as self-heal and heal all. It has been reported to exhibit various biological properties including anti-inflammation, antimicrobial and even anticancer. Selfheal has been widely studied via the use of in vitro studies; as a result, approximately 200 compounds have reported to be isolated from it, many of which have been characterised as triterpenoids, sterols and flavonoids, followed by coumarins, phenylpropanoids, polysaccharides and volatile oils. A study was conducted, from which it can be concluded that that Selfheal has a great activity against Ebola virus and has the potential to be developed as a novel antiviral approach against this infection. This natural Chinese herb merits further investigations as an antiviral due to the promising results observed in its antiviral properties. Upon further research, these antiviral properties may also show efficacy against SARS-COV-2.
The spike of Prunella vulgaris, also known as Prunellae Spica, is often used for the prevention and remedy of various diseases, in traditional Chinese medicine. Prunellae Spica contains various bioactive compounds within its chemical composition including triterpenes, flavonoids, phenolic compounds and carbohydrates. These compounds have been associated with a variety of protective effects such as anticancer, anti-inflammatory, neuroprotective, immunosuppressive activity and anti-HIV activity. In regard to Prunellae Spica antiviral effects, one study demonstrate the great antiviral potential that Prunella has against viral infections such as herpes simplex virus and raises the questions whether similar effects could be demonstrated on viral infections such as COVID-19.
Garlic (Allium sativum) is an aromatic herbaceous plant that has been extensively used worldwide, especially in the Far East, for centuries, in many food dishes due to its appetising property, bitter taste and the flavour it gives to dishes. Despite the use of garlic being such a common practice, this particular plant is of great medical importance, as garlic has exhibited antibacterial, antiviral, antifungal and even antitumor effects. With more than 200 chemical substances, garlic has the ability to protect the human body from many illnesses. Despite researchers arguing in order for garlic to be effective, it should be consumed fresh; some research has proven that the effects of garlic are consistent when it is cooked, with oils even providing better protection against oxidative stress and infections. Garlic is rich in alliin, allicin, ajoenes, vinyldithiins and flavonoids such as quercetin, all of which are sulphur-containing phytoconstituents. Very little work has been done to investigate the antiviral properties of garlic but the experiments that have been conducted have shown that it is effective against influenza B, herpes simplex viruses, cytomegalovirus, rhinovirus, HIV, HSV type 1 and 2 and viral pneumonia. It has been speculated that in the case of HIV, the ajoene acts by inhibiting the integrin-dependent processes, thus inhibiting the fusion of cells with HIV-infected cells, and ajoene was also able to inhibit HIV replication, further showing its antiviral activity. Additionally, a single clinical trial reported that garlic may prevent the occurrence of the common cold, however, the data provided are insufficient. Moreover, it has been scientifically proven that garlic is effectively used in cardiovascular diseases by regulating blood pressure, with reducing effects on glycaemia and high blood cholesterol. Taken together, the data show the beneficial effects extracts of garlic have and thus make it useful in medicine. However, further research is still required to determine the exact mechanisms and its potential as an antiviral agent.
In addition to garlic, ginger, also known as Zingiber officinalis, has shown great promise as a medicinal agent. Ginger is a commonly used spice that is rich in terpenes, polysaccharides, lipids, organic acids, raw fibres and phenolic compounds. It has been reported that the health benefits of ginger are mainly due to the phenolic compounds such as gingerols and shogao it possesses. Many investigations have demonstrated that ginger possesses a range of biological activities such as antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, cardiovascular protective and antiviral properties. In 2016, researchers tested the antiviral effects of ginger against feline calicivirus, a surrogate of human norovirus. The results from this study showed that in addition to garlic, ginger extracts significantly inhibited the calicivirus which was in a dose-dependent manner, thus confirming the specific viral potency ginger possesses. In addition, in a separate study, it was found that fresh ginger had the potential to inhibit the attachment and internalisation of the human respiratory syncytial virus (RSV) to both human lung cells and liver cells, in a dose-dependent manner. It was also found that the treatment with ginger stimulated the mucosal cells to increase sections on Interferon-beta (INF-β) secretions, which has antiviral effects and thus possibly contributed to the inhibition of the viral infection.
Thus, ginger may have the potential to become a promising natural antiviral agent; however, in order for this to happen, further investigation is still required.
It is becoming widely known that different mushrooms possess a variety of biological and pharmacologically active molecules. Previous research has shown that bioactive components and extracts derived from mushrooms exhibit strong anticancer activities. In addition, extracts from mushrooms have also been shown to display antibacterial, antiviral, anti-inflammatory, antiatherogenic and hepatoprotective effects. Thus, mushrooms have a great potential for use as successful antiviral treatments with a reduced chance of adverse side effects.
A study conducted in 2018, determined the structural characterisation of lentinan from shiitake mycelia (Lentinus edodes) as well as looking at the antiviral activity against infectious hematopoietic necrosis virus. The results indicate the antiviral activity of lentinan and its regulation of the innate immune response. As previously said, the innate immune response is a critical factor for COVID-19 disease severity and disease outcome. COVID-19 patients exhibit high titres of inflammatory cytokines and so the effects of lentinan extracted from shiitake should be considered on SARS-COV-2.
Another species of mushroom that has shown promising antiviral effects is Grifola frondosa, (hen-of-the-woods, ram’s head and sheep’s head). This is an example of an edible mushroom that has been used in herbal medicine. In comparison to the shiitake mushroom, Grifola frondosa has a higher nutritional value. The major biologically active component of the mushroom is the β-glucan. Chemicals in Grifola frondosa have shown great anticancer potential with it being approved as a therapeutic drug for the treatment of cancer in China. There has been a study, which showed different results: 9 patients displayed an increase in viral load, whereas a decrease was observed in the viral load of 10 patients. Despite this, 85% of patients reported an increase in sense of wellbeing with regard to symptoms and also secondary diseases that are linked to HIV, further suggesting the positive impact this extract can have against viral diseases.
Abu-Serie et al. evaluated the antioxidant and the anti-inflammatory effects of Malaysian Ganoderma lucidum water extract and Egyptian Chlorella vulgaris ethanolic extract. The main finding of this study shows that two extracts together exhibited higher antioxidant and anti-radical effects in comparison to individual extracts. They also attenuated lipopolysaccharide-induced inflammation and oxidative stress in white blood cells, which occurred through the process of downregulating inflammatory mediators. In addition, the combined extracts also exhibited great ability in enhancing the cellular antioxidant indices. These changes caused by Ganoderma lucidum and Chlorella vulgaris extracts also led to suppression of cellular increase in nitric oxide and lipid peroxidation. This study also concluded that the combined extract had an antioxidant effect that was significantly greater than that of a commercial anti-inflammatory drug, dexamethasone. As oxidative stress and inflammation are two factors that are consistently linked to the pathogenesis of COVID-19, there may be a great possibility of this combined extract as an alternative treatment.
A potential candidate against the SARS-COV-2 virus may be the Chaga mushroom (Inonotus obliquus). It commonly grows in Asia, Europe and North America and is widely used as a raw material in various medical conditions. Chaga has been widely used in traditional medicine to facilitate breathing in Asia and even some parts of Europe, as the mushroom has been known to cause a reduction in nasopharyngeal inflammation. It has been suggested that Chaga mushrooms possess a powerful enzymatic system and a strong system of defence, due to their parasitic mode of life. Extracts from this fungus have been used for its antitumor, antioxidant, hepatoprotective and anti-inflammatory properties. Moreover, water extracts from Chaga have traditionally been used as a source of bioactive compounds that exhibit cytostatic and cytotoxic effects, and this has led to the manufacturing of such compounds in the form of a nontoxic aqueous extract called Befungin. Insight into the connection between Chaga mushroom and its antiviral effect has been proven to be promising. A study demonstrated the effect of Chaga polysacharides in cats with feline viruses including feline calcivirus, feline herpesvirus 1, feline influenza virus, feline infectious peritonitis virus and feline panleukopenia virus. Inhibition of RNA viruses and DNA viruses in all the five viral subtypes was observed. Suppression of the infectivity of pandemic influenza virus was also noted in mice and it was observed that this mushroom is comparable to Tamiflu, an antiviral drug that inhibits viral reproduction. Additionally, another study looked at the antiviral effect of Chaga against Herpes simplex virus and found that the Chaga extract led to an overall reduction in this infection in Vero cells.
Despite many advancements in science, no effective vaccine or specific therapy has been approved for humans against SARS-COV-2, and so there is an urgent need to develop therapeutic treatments against these threats. Traditional Chinese medicine holds an exclusive position among the variety of traditional medicines because of its thousand-year history. The extracts described in this review have been proven to possess great antiviral activities, with a general consensus of low toxicity. In addition, compared to commercial pharmaceuticals, such medicinal herbs are readily available and much cheaper. With the current pandemic, many scientists have rushed to the development of a potential vaccine and therapeutic agent that is effective against COVID-19; however, herbal agents should not be overlooked. The data presented in this review show the promising effects many herbs and mushrooms have against a variety of viral infections. This review has highlighted the therapeutic potential of Chaga as a natural antiviral treatment against SARS-COV-2. Earlier studies into this mushroom have laid the groundwork into the antiviral capabilities of Chaga, however further research into characterising the bioactive ingredients, understanding the underlying mechanisms as well as assessing the efficacy and potential application in vivo should be encouraged in order to develop an effective antiviral treatment against COVID-19. Until the present time, there has not been much research regarding the potential of natural agents against COVID-19, thus opening the research into this field may unlock the potential such extracts may have against SARS-CoV-2.