INTERNATIONAL JOURNAL OF FUNCTIONAL NUTRITION 1: 6, 2020
Abstract. The global pandemic caused by the novel coronavirus
disease 2019 (COVID‑19), for which there is no effective vaccine
or treatment available yet, has led to a global health emergency.
Despite a lack of clinical data, compelling evidence from the
literature suggests that certain nutraceuticals (such as omega‑3
fats, β‑glucans, amino acids, probiotics, vitamins and minerals)
and plant‑based compounds derived from herbal extracts may
potentially be used in the treatment of COVID‑19. In the present
review article, the benets of such natural products in treating
various respiratory complications are highlighted, and it is
tentatively suggested that these benets could be extrapolated to
COVID‑19. These natural compounds may not only modulate
the immunity of a susceptible population, but may also pave the
way towards the development of drugs which may be used to treat
COVID‑19. Although attention has recently focused on these
compounds in this context, further clinical and experimental
studies are required to validate their efcacy. It is thus suggested
that the in vitro and in vivo evaluation of these compounds be
carried out as soon as possible, in order to counteract the ongoing
increase in the number of cases of COVID‑19.
Contents
1. Introduction
2. Therapeutic benefits of nutraceuticals for respiratory
complications
3. Therapeutic benefits of herbal extracts for respiratory
complications
4. Conclusion
1. Introduction
Coronavirus disease 2019 (COVID‑19). Global health is
threatened by an ongoing outbreak of COVID‑19, a respiratory
disease caused by the novel coronavirus, SARS‑CoV‑2, which
was rst identied in December, 2019 in Wuhan, China (1). As
of August 28, 2020, >24.7 million individuals had been infected
with the virus worldwide, and approximately 838,000 have
succumbed to the disease (2). In total, seven types of coronavi‑
ruses, namely severe acute respiratory syndrome coronavirus
(SARS‑CoV), Middle East respiratory syndrome coronavirus
(MERS‑CoV), severe acute respiratory syndrome corona‑
virus 2 (SARS‑CoV‑2), OC43, NL63, 229E and HKU1, are
known to infect humans. Of these, the rst three can cause
fatal infections, whereas the latter four typically cause mild
common cold‑associated symptoms, particularly in immuno‑
compromised individuals (3). COVID‑19 is highly contagious
and infected patients exhibit symptoms of fever, pneumonia,
thrombocytopenia, cough, dyspnea, myalgia and asthenia (4).
Prevention and treatment of COVID‑19. As of August 5, 2020,
no vaccine or successful treatment for COVID‑19 has been
reported and only supportive care, personal protection, early
diagnosis and isolation are available to reduce the spread and
severity of the infection (5). Huang et al (6) reported that pat ients
with COVID‑19 develop acute respiratory distress syndrome,
followed by anemia, acute heart injuries and secondary
infections. Empirical therapy with antibiotics (including ceph‑
alosporins, azithromycin, vancomycin, quinolones, tigecycline
and carbapenems), antivirals (including lopinavir, ritonavir,
remdesivir and oseltamivir) and corticosteroids (including
dexamethasone and methylprednisolone) has thus been used
for the treatment of patients with COVID‑19 (7). The clinical
efcacy of all of these treatments, however, warrants further
conrmation.
Potential agents with which to combat COVID‑19. Research
proposals and clinical trials have suggested that some treat‑
ments, including supplements and phytochemicals, have
the potential to help fight coronavirus infection. A recent
study suggested that the risk of becoming infected could be
reduced by vitamin D3 supplementation. Serum concentra‑
tions >40‑60 ng/ml (100‑150 nmol/l) were suggested to be
Nutraceuticals and herbal extracts: A ray of hope
for COVID‑19 and related infections (Review)
AHMED HAMZA TAHIR1, MUHAMMAD MOHSIN JAVED2 and ZAHID HUSSAIN3
1Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Punjab 54590;
2Ofce of the Registrar, Virtual University of Pakistan, Lahore, Punjab 55150; 3Institute of Industrial Biotechnology,
Government College University, Lahore, Punjab 54000, Pakistan
Received May 16, 2020; Accepted August 27, 2020
DOI: 10.3892/ijfn. 2020.6
Correspondence to: Mr. Ahmed Hamza Tahir, Institute of
Biochemistry and Biotechnology, University of the Punjab,
Quaid‑i‑Azam Campus, Canal Road, Lahore, Punjab 54590,
Pakistan
E‑mail: ahmedhamzatahir@yahoo.com
Key words: coronavirus, COVID‑19, human health, nutraceuticals,
herbal, phytochemicals, natural products
TAH IR et al: USE OF NUTRACEUTICALS AND HERBAL EXTRACTS AGAINST COVID‑19 AND RELATED INF ECTIONS
2
required in order to prevent infection, with even higher doses
required to treat patients already infected (8). In addition,
due to its antiviral and immunomodulatory properties, zinc
supplementation may also be considered for use in the preven‑
tion or treatment of COVID‑19 (9). Zhang et al (10) proposed
that melatonin, which has antioxidant and anti‑inammatory
properties, together with a good safety profile, and also
potentially modulates the immune system, improves sleep
quality, and reduces vessel permeability, anxiety and the use
of sedatives, may lead to better clinical outcomes for patients
with COVID‑19. Ang et al (11) analyzed the potential of tradi‑
tional herbal medicines, which contained a total of 56 herbs,
for the treatment of patients with COVID‑19. The detailed
review by Islam et al (12) also reported that a wide range of
herbal compounds, including tylophorine, lycorine, ouabain,
silvestrol, homoharringtonine and 7‑methoxycryptopleurine,
broadly suppressed different coronaviruses, with IC50 values
ranging from 12 to 143 nM. Yu et al (13) also demonstrated
that the plant‑derived flavonoids, myricetin and scutella‑
rein, are inhibitors of SARS‑CoV helicase. Collectively, the
above‑mentioned studies suggest that natural products and
dietary supplements may help in the ght against COVID‑19.
A pictorial representation of the potential benecial effects
of nutraceuticals and herbal extracts against COVID‑19 is
depicted in Fig. 1.
SARS, SARS‑CoV‑2 and MERS are known as enveloped
viruses (14), and several bioactive lipids, including omega‑3
fatty acids, such as eicosapentaenoic acid (EPA) and doco‑
sahexaenoic acid (DHA), have been reported to inactivate
these enveloped viruses and reduce their proliferation (15).
Some metabolites of EPA and arachidonic acid, such as
thromboxanes, leukotrienes and prostaglandins, induce
inflammation (16), whereas other metabolites of EPA and
DHA, such as maresins, protectins, resolvins and lipoxins,
suppress inammation, modulate the T‑cell response, reduce
microbial load, augment phagocytosis and enhance wound
healing processes. These latter bioactive lipids can be used
in the treatment of airway inammation and common human
lung diseases, such as chronic obstructive pulmonary disease
(COPD) and asthma (17,18). A recent study revealed that both
EPA and DHA, from sh oil, improved breathing for patients
with asthma (19). The oral or intravenous administration
of EPA or DHA could, therefore, potentially promote the
recovery of patients with COVID‑19 (20).
With regards to the recent increase in the number of
published articles on COVID‑19, including reports of infected
cases, fatalities, disease severity and vulnerability (21), the
purpose of the present review article is to draw the attention
of medical and pharmacy professionals towards nutraceuticals
and herbal extracts for the treatment of COVID‑19. The present
review focuses on reported facts and gures to highlight the
potential of natural products to strengthen the immunity of
the general population, and to pave the way for the identica‑
tion of drugs which may be used in the treatment of patients
with COVID‑19. Mathematical models predict that reported
numbers of cases of COVID‑19 will continue to increase until
a vaccine is made available to the global market (22). The
present review article highlights the therapeutic signicance of
some promising natural products with activity against viruses
in general, and COVID‑19 in particular.
2. Therapeutic benets of nutraceuticals for respiratory
complications
Vita mins. A daily intake of 20‑50 µg of vitamin D was
recently recommended for obese individuals, healthcare
workers and smokers in order to enhance their resistance
to COVID‑19 infection (23). Yalaki et al (24) reported that
supplementation with vitamin D in patients suffering from
acute bronchiolitis increased immunity and normalized
pulmonary function. Other studies have also associated the
administration of vitamin D with the reduced likelihood of
developing respiratory infections (25,26). The administra‑
tion of high‑dose vitamin C (1,000‑6,000 mg) has also been
reported to decrease the time spent by critically ill patients on
mechanical ventilation by 25%, and also reduced their length
of stay in an intensive care unit (27). Of note, vitamin C has
also been proven to be effective against asthma induced by the
common cold (28,29).
Dietary minerals
Selenium. The importance of selenium for optimal immune
function has been emphasized in the literature (30). Selenium
provides resistance against viral infections through its redox
homeostasis and antioxidant properties (31). Selenium de‑
ciency has been associated with impaired immune function,
likely due to increased oxidative stress in the host organism (32).
This can lead to alterations in the viral genome, which may
increase virulence and boost pathogenicity (33). Dietary
selenium has been shown to improve immunity against the
lethal H1N1 inuenza virus infection (34‑36) and can also be
potentially used in the current battle against COVID‑19 (37).
Zinc. Elderly individuals are often decient in zinc, which
is essential for immune function, and zinc deficiency is
considered to be a potential risk factor for the development
of pneumonia among the elderly (38,39). Barnett et al (40)
found that older subjects with higher serum zinc concentra‑
tions (>70 µg/dl) were not only characterized by a lower
incidence of pneumonia (P<0.001), but also with a lower dura‑
tion of disease and less need for antibiotics than older patients
with low serum zinc concentrations (<70 µg/dl). Other studies
have demonstrated that zinc deciency is associated with an up
to 80% higher incidence of pneumonia in children (41,42) and
zinc supplementation has also been reported to signicantly
decrease the development of respiratory diseases among
children suffering from acute lower respiratory tract infec‑
tions (43). A previous in vitro study also indicated that zinc
salts inhibited the replication of respiratory syncytial virus
(RSV) and prevent cell‑to‑cell spread in human epithelial
type 2 (HEp‑2) cells (44). Zinc is considered to be essential
for the respiratory epithelium due to its anti‑inammatory
and antioxidant activities, along with its ability to regulate
tight junction proteins, including claudin‑1 and Zonula
occludens‑1 (45,46). In a separate study, the length of cilia at
the bronchial epithelium of zinc‑decient rats was shown to be
improved by zinc supplementation (47). In vit ro experiments
in the study by Woodworth et al (48) highlighted the ability
of zinc to boost mucociliary clearance by enhancing the beat
frequency of cilia. Zinc ions have also been found to inhibit
the RNA‑dependent RNA polymerases of influenza virus,
hepatitis C virus (HCV) and rhinoviruses, and to impair the
INTERNATIONAL JOURNAL OF FUNCTIONAL NUTRITION 1: 6, 2020 3
activity of the RNA‑synthesizing machinery of nidoviruses,
the order of viruses to which SARS‑CoV‑2 belongs (49,50).
Iron. Whereas excessively high serum concentrations of
iron can cause oxidative stress and lead to viral mutations, iron
deciency can impair host immunity and increase suscepti‑
bility to infections (51). The dysregulated homeostasis of iron,
which alters serum concentrations, has been associated with
several respiratory diseases, including asthma, cystic brosis,
COPD, idiopathic pulmonary brosis, acute respiratory tract
infections and lung cancer (52,53). The strict regulation of
serum iron concentration could thus provide favorable clinical
outcomes for patients with COVID‑19.
N‑acetyl‑cysteine (NAC). NAC, which is derived from the
naturally occurring amino acid, cysteine, is most commonly
prescribed to patients suffering from various respiratory
complications, including respiratory tract infections, idiopathic
pulmonary brosis and chronic bronchitis (54‑56). The anti‑
oxidant and mucolytic effects of NAC have been reported to
signicantly improve the function of airways and to reduce
COPD exacerbations (57). NAC t reatment has also been reported
to inhibit the RSV infection of human alveolar epithelial (A549)
cells and to reduce mucin release (58). In a previous review
article, Sadowska (59) concluded that NAC may be benecial
in the management of COPD, since it would promote clearance
of mucus and alleviate oxidative stress and inammation. Ta ken
together, these results demonstrate the clear potential of NAC as
an adjuvant supplement for COVID‑19 patients (60,61).
Amino acids
Arginine. Arginine has been reported to act synergistically with
virucidal conditions, such as high temperatures and acidic pH
levels, and can thus potentially inactivate enveloped vir uses (62,63).
Tsuji m oto et al (64) successfully inactivated herpes simplex virus
type 2 (HSV‑2) using a solution of arginine. Similarly, inuenza
A has been shown to be inactivated under similar conditions (65).
Recently, Meingast and Heldt (63) suggested that arginine inac‑
tivates viruses through a variety of mechanisms, including pore
formation and destabilization of the viral membrane, the inhibi‑
tion of the function of non‑structural proteins, the suppression
of protein‑protein interactions and aggregation. Ikeda et al (66)
suggested that arginine associates with multiple sites on viral
particles, thereby affecting glycoprotein‑lipid interactions on the
viral envelope. Due to the low cytotoxicity of arginine, a previous
study demonstrated the possible use of an intranasal spray
containing an aqueous solution of arginine to inhibit inuenza
A infection in vivo (67). In a NC/Nga mouse model of asthma,
arginine was found to contribute to improved asthmatic symp‑
toms by reducing airway inammation in lung tissue and altering
L‑arginine metabolism (68).
Figure 1. Schematic diagram illustrating the potential benecial effects of nutraceuticals and herbal extracts in the management of COVID‑19.
TAH IR et al: USE OF NUTRACEUTICALS AND HERBAL EXTRACTS AGAINST COVID‑19 AND RELATED INF ECTIONS
4
Glutamine (GLN). GLN is one of the most abundant free
amino acids within the human body, with a concentration of
approximately 500‑900 µmol/l (69). In a murine model of
asthma, Lee et al (70) demonstrated that, at therapeutic doses,
GLN suppressed inammation by inhibiting the recruitment
of neutrophils into the airways. In a ventilator‑induced lung
injury (VILI) mouse model, in which the lungs of mice are
acutely injured by acid aspiration, the administration of GLN
was reported to reduce the destruction of lung tissue, lung
edema, cytokine production and neutrophil recruitment to the
lung (71). Oliveira et al (72) proposed that exogenous GLN
may be benecial against asthma and acute respiratory distress
syndrome (ARDS), and during the treatment of lung cancer.
Thus, GLN may provide therapeutic benets to COVID‑19
patients (73).
Probiotics. Nutritional supplementation with probiotics has
been reported to be beneficial for patients suffering from
respiratory tract infections (74‑76). Strasser et al (77) reported
that various strains of probiotics, including Lactococcus lactis
W58, Lactobacillus brevis W63, Enterococcus faecium W54,
Lactobacillus acidophilus W22, Bidobacteriumlactis W51
andBidobacterium bidum W23, helped to reduce the inci‑
dence of upper respiratory tract infections (URTIs) in trained
athletes, without altering performance. Another probiotic strain,
Lactobacillus casei Zhang, which exhibits immunomodulatory,
anti‑inammatory and anti‑oxidative effects, has been shown to
alleviate the symptoms of URTI and restore gastrointestinal hea lth
in adults and elderly subjects (78). RSV infection has also been
reported to be suppressed by various probiotic strains, including
Lactobacillus gasseri SBT2055 and Lactobacillus rham‑
nosus CRL1505 (79,80). The results of the meta‑analysis by
Kang et al (81) revealed the efcacy of probiotics in the treatment
of common cold infections. During the COVID‑19 pandemic,
the National Administration of Traditional Chinese Medicine
and the Chinese National Health Commission recommended
the use of probiotic therapy to control coronavirus infection (82);
however, the effectiveness of probiotics in reducing the mortality
rate of patients in intensive care units remains uncertain.
Jayawardena et al (83) suggested the use of probiotics as a dietary
supplement to prevent infection of susceptible populations with
SARS‑CoV‑2. Since probiotics are readily available as dietary
supplements and have negligible side‑effects if administered at
the correct doses, they may thus provide a useful intervention
strategy against COVID‑19 (84‑86). A study to evaluate whether
dietary supplementation with Lactobacillus coryniformis
K8 can help to prevent healthcare workers from contracting
COVID‑19 was registered at ClinicalTrials.gov (NCT04366180)
on April 28, 2020.
Omega‑3 fatty acids. Fats, which can be classied as saturated
or unsaturated, form an essential pa rt of the human diet and play
a vital role in nutrition and health (87,88). Fats serve as a main
source of energy, participate in cell signaling and responses,
and play a structural role as part of the cell membrane.
Omega‑3 polyunsaturated fatty acids have been reported to
confer health benets in patients suffering from respiratory
complications, such as ARDS, COPD, impaired oxygenation
and pulmonary brosis (89‑92) and are attracting consider‑
able attention due to their anticoagulant properties and ability
to reduce inammation (93). The consumption of omega‑3
polyunsaturated fatty acids has been associated with a number
of physiological alterations, including the production of lung
surfactants, host‑microbial interactions, alterations in blood
rheology and the production of endogenous eicosanoids (94).
According to the study by Miyata and Arita (95), omega‑3
fatty acids can alleviate the inf lammatory complications
resulting from allergic reactions and asthma. Omega‑3 fatty
acids have also been reported to suppress the synthesis of
immunoglobulin E, leading to reduced airway inammation
and bronchoconstriction in patients with asthma (96). The
lipid mediator, protectin D1, which is derived from omega‑3
fatty acids, has been reported to suppress the replication of the
highly pathogenic inuenza H5N1 virus, and to improve the
survival of H5N1‑infected mice (97). Linday et al (98) found
that the simultaneous administration of cod liver oil (which
contains EPA and vitamin A) and a multivitamin‑mineral
supplement to children led to a statistically significant
(P<0.05) decrease in the mean number of URTI‑related
medical consultations over time. Overall, omega‑3 fatty
acids confer signicant health benets to patients with URTI
complications and shorten the length of stay of acutely ill
patients in hospital (99‑101). Since omega‑3 fatty acids have
proven to be effective in reducing airway inammation and
bronchoconstriction, have also exhibited efcacy against viral
infections (102,103), their potential for use against COVID‑19
warrants further investigation (104‑106).
β‑glucans. β‑glucans, which are potent activators of
immune cells, including neutrophils, natural killer cells and
macrophages, exert a favorable effect on the host defense
system (107). In addition to the immunomodulatory effects,
the administration of β‑glucans has been shown to reduce the
susceptibility of healthy subjects to URTIs and to decrease the
severity of URTIs in infected subjects (108‑111). β‑glucans
have also been shown to exhibit antiviral activity against
HSV‑1 (112,113) and inuenza virus (114,115). More recently,
it was suggested that β‑glucans can help to reduce morbidity
and mortality associated with COVID‑19 (116,117).
3. Therapeutic benets of herbal extracts for respiratory
complications
The use of phytochemicals and natural products for the treatment
of various diseases is gaining worldwide attention (118,119). Prior
to the discovery of antibiotics, herbal extracts played an important
role in the treatment of diseases (120), and puried natural prod‑
ucts and herbal extracts now provide a rich pool of compounds
for the development of novel antiviral drugs (121). Lin et al (122)
summarized the antiviral activity of various natural products and
herbal medicines against some notable viral pathogens, including
RSV, measles virus, dengue virus, influenza virus, human
immunodeciency virus (HIV), HSV, HCV, hepatitis B virus,
enterovirus 71, coxsackievirus and coronavirus.
Cheng et al (123) examined the activity of naturally occur‑
ring triterpene glycosides (saikosaponins A, B, C and D),
extracted from medicinal plants, such as Bupleurum spp.,
Scrophularia scorodonia and Heteromorpha spp., against
coronaviruses. They found that the tested phytochemicals
significantly inhibited the early stage of human coronavirus
INTERNATIONAL JOURNAL OF FUNCTIONAL NUTRITION 1: 6, 2020 5
229E infection by interfering with viral replication, absorption
and penetration. In 2008, Lau et al (124) demonstrated that an
aqueous extract of the medicinal herb, Houttuynia cordata,
facilitated the clearance of SARS‑CoV infection in mice, both
by improving the immune response and by a direct antiviral
effect. Firstly, it stimulated cell‑mediated immunity and,
secondly, it attenuated viral replication by inhibiting pivotal viral
enzymes (RNA‑dependent RNA polymerase and 3CL protease)
involved in the replication process. Another traditional herb,
Pelargonium sidoides, has been tested clinically as a treatment
for human coronavirus, inuenza A virus (H1N1 and H3N2),
RSV, coxsackievirus, parainuenza virus, coughs, URTIs and
gastrointestinal conditions (125‑128). Licorice extract, derived
from the root of Glycyrrhiza glabra, has been shown to exhibit
in vitro activity against vesicular stomatitis virus, vaccinia
virus, SARS‑CoV, RSV and HIV‑1 (129,130). Nigella sativa,
also known as black seed, has emerged as a ‘miracle’ herb, with
potential antidiabetic, antioxidant, anticancer, anti‑inammatory,
bronchodilatory, immunomodulatory and pulmonary‑protective
activities (131,132). In 2005, Li et al screened >200 Chinese me dic‑
inal herbs for activity against SARS‑CoV and found that herbal
extracts from four medicinal plants, namely Lindera aggregata,
Pyrrosia lingua, Lycoris radiata and Artemisia annua, exhibited
antiviral activity (133). Further fractionation and purication of
the L. ra diata extract identied lycorine as a potential candidate
for the development of new anti‑SARS‑CoV drugs (133). Equally
importantly, Cordyceps (medicinal mushrooms) have signicant
potential to strengthen the cardiovascular, respiratory and
immune systems, and also have general antiviral and antioxi‑
dant properties (134‑136). The medicinal and health‑promoting
attributes of therapeutic fungi have recently gained considerable
attention in the eld of COVID‑19 research (137‑139).
4. Conclusion
The present review attempted to highlight the potential of
various nutraceuticals and herbal extracts as possible treatments
for COVID‑19. Although strong evidence for the potential of
these compounds to combat the ongoing COVID‑19 pandemic
has already appeared in the literature, new evidence is gradually
emerging (140). The reported clinical data are, however, still
inconclusive and there are also inconsistencies within the data,
since some clinical studies did not achieve the desired effects.
These inconsistencies seem to be related to a number of factors,
including the dose used, the heterogeneity of the target popula‑
tion, the plasma concentration, the beginning and duration of
the treatment and the route of administration (141). Taking these
factors into consideration, randomized and controlled trials
are required to resolve these controversies and to clarify issues
around the use of these compounds. In addition to an increase
in the reported number of cases, some patients who have recov‑
ered from coronavirus are testing positive again (142). Clinical
validation of compounds that could possibly help to combat the
COVID‑19 pandemic is thus urgently required.
Acknowledgements
The authors would like to thank International Science Editing
(http://www.internationalscienceediting.com) for providing
free language‑editing services for this article.
Funding
No funding was received.
Availability of data and materials
Not applicable.
Authors' contributions
AHT and MMJ conceived this review. AHT wrote and revised
the manuscript. All authors read and approved the nal version
of the manuscript.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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