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ASIAN JOURNAL OF PHARMACOGNOSY
Asian J. Pharmacogn 4(4): 32-52
© 2020, Asian Society of Pharmacognosy. All Rights Reserved.
eISSN-0128-1119
32
Herbal remedies and COVID-19: where is the evidence?
Seithikurippu R. Pandi-Perumala,*, Rajendra P. Mauryab, Dinesh
Chandrac, Shalini Mauryab, Om P. Singhe, Rajneesh A. Tripathif,
Yogesh C. Tripathig, Arup Girih, Vijay K. Bhartih
aSomnogen Canada Inc., College Street, Toronto, ON, Canada
bRegional Institute of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi –
221005, India
cDepartment of Zoology, Government PG College, Pilibhit, Uttar Pradesh, India.
dDepartment. of Kayachikitsa, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University,
Varanasi, UP, India.
eShri Jagdish Prasad Jha Barmal Tibrewala University, Jhunjhunu, Churu Rd, Vidyanagari, Churela 333001,
Rajasthan, India.
fDivision of Chemistry and Bioprospecting, Forest Research Institute, Dehradun 248006, India.
gDRDO-Defence Institute of High Altitude Research (DIHAR), Leh-Ladakh-194101, India.
*For correspondence: Pandiperumal2020@gmail.com
_______________________________________
Abstract: The novel coronavirus disease 2019 (COVID-19) was widely regarded due to an
unpredictable, imminent pandemic posing a significant threat to humanity. This new virus has high
infectivity, mortality, and variable latency. The recurrent modification in the virus' genetic
(antigenic) structures poses a challenge in successful vaccine development. While several vaccine
trials are underway, many conventional drugs are repositioned (i.e. repurposing) and used for
prophylactic and therapeutic purposes. However, the results were not very encouraging and often
causing serious adverse effects. To come down the grimness and duration of acute disease and
complexities, safe alternative remedies are, thus, needed. In symptomatic SARS-COV-2 patients, the
traditional Chinese medicine (TMC) with allopathic drugs and Moroccan medicinal plant extract
showed significant benefit. Traditional medicine derived from Indian herbal plants used since
ancient times to treat human diseases in India is easily available and cost-effective without any side
effects. Some compounds from Indian herbal plants such as phytonutrients, flavonoids,
phytomelatonin, and others have been demonstrated to possess anti-inflammatory,
immunomodulatory, and antiviral bioactivities. In this review, we discuss some of the potential
herbal plants with antiviral properties based on the history of usefulness in either treating COVID-19
or other potential viral infections. Considering the benefits of these preparations, government
agencies must take interest in these preventive therapies and allot more funding. More evidence-
based, experimental (basic, translational, and clinical) studies are needed to establish its efficacy and
safety of these ingredients either alone or in combination.
Keywords: Antioxidants, antiviral, COVID-19, herbal, immunoenhancement, plants, virus
© 2020, Asian Society of Pharmacognosy. All Rights Reserved.
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Asian J. Pharmacogn 4(4): 32-52
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INTRODUCTION
The world community faces an unheard-of pandemic of new coronavirus disease (COVID-
19) caused by Coronavirus 2 Severe Acute Respiratory Syndrome (SARS-CoV-2). One report on
April 8 2020 stated that about 1.43 million people were infected and 82,100 casualties occurred. The
number of infected and deaths were increasing day by day despite taking all the preventive measures
in all the infected country except the lack of therapeutic medicine. The Coronavirus infection is now
caused by the deadly situation throughout the globe after its pandemic nature. While officially
licensed pharmacological agents are not yet available for COVID-19 therapy, several international
health agencies are actively interested in clinical trials of different compounds [1–4]. Moreover,
among the immigrant community and ethnic minorities, it is not unusual to try cost-effective
"alternative" therapies to avoid or treat COVID-19. Some of these supposed remedies include, but
are not limited to, herbal therapies like Ashwagandha, Artemisia annua, Capsaicin, Curcumin,
Favipiravir, Guduchi (Tinospora cordifolia), Kabasurakudineer (Table 1), Vitamin C, Vitamin D, and
Zinc. Homeopathic formulations such as Arsenicum Album 30 (Ars Alb 30C) and Camphor 1 m are
used as anti-COVID-19 prophylactic agents. Other compounds used as prophylactics were tested
either alone or in combination, assessing their effectiveness and safety as a potential antiviral agent.
Such compounds include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, metformin
[5,6]. So far, the therapeutic and investigative approaches for COVID-19 have focused primarily on
agents for attacking or immunizing against the virus. Most of the antiviral and herbal drugs in
COVID-19 are important because of their antioxidant and immunomodulatory properties.
However, every medical specialty claims they have some help available to either prevent,
treat, or cure potential infectious viral pathogens. This includes, but is not limited to, Siddha,
Ayurveda, Unani, complementary and alternative medicine (CAM) therapies, and indigenous tribal
preparation around the world [7]. Besides, there are many unproven and fraudulent claims
concerning prevention, cure, and management for COVID-19. When patients and consumers resort
to any of these alternative treatment modalities, care must be taken to avoid side effects and/or
potential death. The health agencies such as the World Health Organization (WHO) has released
warning against the use of unproven treatment [8]. Hence, patients and consumers are advised to
consult appropriate medical specialties and avoid self-medication. As CAM therapies evolving due
to some factors and lacunae in the health care system, more research is needed on this front (Fig. 1).
In our report, we have highlighted some of these available options mainly CAM therapies that need
to be researched further.
This review reveals the outbreak of the coronavirus pandemic, the mechanism of infection,
and finding the most suitable medicinal plants from the floral diversity of South Asian countries.
From ancient times, many medicinal plants are being used for different diseases including thse viral
infection also. The recent pharmacology industry also mainly depends upon the plant-related drug
formulation for most of the evolved diseases in the globe. Therefore, with preventive measures such
as the use of hand sanitizer, washing hands, social distance, etc., to fight with this pandemic, now,
the time for therapeutic drug development. The cognition of medicinal plants, which have the
antiviral properties, may be applicable for the new drug formulation or may consume at the society
level to make the human immune system strong.
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Table 1 The composition of Kabasurakudineer, an herbal concoction.
The composition of KabaSuraKudineer, a herbal concoction
Botanical name
English
name
Plant part being used
Zingiberofficinale
Ginger
Rhizome, ginger root or ginger
Piper longum
Indian long pepper or
Pipli
Dried fruit
Syzygiumaromaticum
Cloves
Flower bud
Tragiainvolucrata
Indian stinging nettle
Root
Anacyclus pyrethrum
Pellitory,
Spanish
chamomile, or Mount
Atlas daisy or Akarkara
Root
Solanumanguivi
Forest Bitterberry or
African Eggplant
Root
Terminalia chebula
black
-
or
chebulicmyrobalan
Small, ribbed and nut
-
like fruit rind
Justiciaadhatoda
Malabar nut, adulsa,
adhatoda
Leaf
Plectranthusamboinicus
(formally known as Coleus
aromaticusBenth.)
Indian mint
Leaf
Saussureacostus
Costus or Kuth
Root
Tinosporacordifolia(Thunb.)
Miers (Guduchi)
Heart
-
leaved moonseed,
Guduchi, orGiloy
Stem
Clerodendrumserratum (L.)
Moon.
Turk's tur
ban moon, Blue
glory, Beetle killer
Root
Andrographispaniculata
Creat or green chireta
Aerial parts
Cissampelospareira L.
Velvet
-
leaf, Abuta
Root
Cyperusrotundus
Coco
-
grass, Java grass,
Nut grass, Red - or Purple
nut sedge, Khmer
kravanhchruk
Root tuber
Preparation of decoction:
An equal part of these 15 ingredients must be made into a coarse powder.8 gm powder in 4-glass
water, boiled and reduced into 1 glass. May be taken twice or thrice according to the severity of
the fever and other respiratory symptoms. Since the recipe is recently promoted as prophylaxis for
COVID-19, for prophylaxis, it may be taken once a day for three days, if required it may be taken
after a gap of 3-4 days. No need to take it continuously.
Etiopathogenesis of COVID-19: Severe acute respiratory syndrome corona virus-2 (SARS-
CoV2) caused novel coronavirus disease 2019 (COVID-19). SARS-CoV2 is a single-stranded, β
coronavirus-containing RNA. Viral host cell infection triggered by endocytosis liaised by the
receptor. Receptor binding domain (RBD) is located in virus spike protein attached to the target cell
via angiotensin-converting enzyme-2 (ACE-2) receptor, which is highly enriched distribution in the
alveolar epithelium in the human lung. An analysis of the structural model shows that SARS-CoV2
has a 10 times more binding affinity than SARS CoV that has a similar spike protein RBD [9]. RBD
ACE-2 complex formation mediates the coalition between the host cell membrane and viral
envelope during virus-host interaction and ultimately grants the viral genome to entry in the host cell
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[10]. Many herbal compounds inhibit infection and propagation of COVID-19 by blocking the
complex RBD ACE-2.
SARS CoV 2 remains unknown to have pathological mechanisms for organ damage.
COVID-19's potential mechanism for ARDS may be immune disruption and inflammatory process.
The peripheral blood examination and quantification of extreme COVID-19 patients with plasma
cytokine have shown depletion of cytotoxic T-lymphocytes and a massive increase in IL-10, IL-6,
IL-2, and IFN-α. This 'cytokine storm' causes damage to the alveolar epithelium and therefore
respiratory distress [11].
Scope of Ayurveda against COVID-19: For nearly 5000 years Ayurveda, an ancient Indian
medicine method, has been practiced in India, relying heavily on plants to formulate it. Ayurvedic
herbal supplements and immunity boosters showing the way to a broad-spectrum antiviral drug that
is the need of the hour. For plants namely Glycyrrhiza glabra, Andrographis paniculata, Phyllanthus spp.,
Zingiber officinale,Withania somnifera, and Curcuma longa antiviral properties have been reported.
Whereas, others have the properties to enhance immunity, such as Tinospora cordifolia and Emblica
officinalis [12]. It has been previously shown that Coptidis rhizome, Meliae cortex, Sanguisorbae radix,
Cimicifuga rhizome, and Phellodendron cortex exhibit anti-coronavirus activity. Sophorae radix, Torilis
fructus, and Acanthopanacis cortex decreased intracellular viral RNA levels with corresponding viral
protein decreases [13]. Therefore, Ayurveda has a tremendous to attenuate this pandemic but the
trials should be implemented substantially which will simplify learning, produce proof, and provide
a way forward [14].
Efficacy of medicinal plants against COVID-19: From ancient times, medicinal plants have been
in use for the treatment and prevention of various diseases including viral infections (Table 2).
Studies on plant antiviral activity, however, were minimal compared with other antimicrobial
efficiencies such as antibacterial and antifungal activities. Some of the plants and plant products
were investigated for their effectiveness against pathogenic viruses in general, and particularly
COVID. Table 2 presents some of the major preventive and prophylactic medicinal plants with
recorded effectiveness against COVID-19.
Research on Vitex trifolia and Sphaeranthus indicus for coronaviral anti-mouse activity reported
inhibiting the NF-kB pathway after reducing the inflammatory cytokines which are involved in
SARS-CoV respiratory distress [59,60]. Clitoria ternatea has the metalloproteinase inhibitory effect in
ACE shredding that is primarily associated with virus replication. Strobilanthes cusia plant reportedly
blocks the HCoV infection [61]. Amber et al. [62] reported that Justicia adhatoda, Verbascum Thapsus,
and Hyoscyamus niger that is traditionally used in bronchitis, have been found to reduce influenza
virus infections. Kambizi et al. [63] demonstrated that Aconitum ferox and Withania somnifera aqueous
extracts have anti-HSV-1 activity.
Thus, several medicinal plants, including Cynara scolymus, Punica granatum, Coscinium
fenestratum, Boerhaavia diffusa, Cassia occidentalis, Embelia ribes, and Coriandrum sativum can inhibit the
activity o ACE [64–66]. One study on Salacia oblonga reported that it has the anti angiotensin II
activity [67]. Andrographis paniculata commonly known as Kalmegh has been credited for its efficacy
against viral respiratory infections [68]. The interleukin-1β molecules, caspase-1, and high NOD-like
receptor protein 3 (NLRP3) were suppressed after the application of this plant [11]. Glycyrrhiza
glabra, Clerodendrum inerme, and Allium sativum have the potential to inactive the viral replication
[69–71].
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Table 2 Medicinal plants having anti-viral properties
Sl. No.
Medicinal Plants
Virus Name
References
Achyranthus aspera
Herpes simplex virus
[15]
Allium cepa
SARS
-
COV2
[16]
Allium porrum
SARS
-
COV2
[17]
Allium sativum
SARS
-
COV2
[18]
Alnus japonica
SARS
-
COV2
[19]
Andrographis paniculata
H1N1,
H9N2, H5N1
[20]
Andrographis paniculata
Dengue virus
[20]
Andrographis paniculata
Dengue virus
[21]
Angelica keiskei
SARS
-
COV2
[22]
Azadirachta indica
Dengue virus
[23]
Betula pubescens
SARS
-
COV2
[24]
Canthium coromandelicum
HIV
[25]
Carissa
edulis
Herpes simplex virus
[26]
Cassiae semen
SARS
-
COV2
[27]
Chamaecyparis obtusavar formosana
SARS
-
COV2
[24]
Cinnamomum cassia
SARS
-
COV2
[28]
Cryptomeria japonica
SARS
-
COV2
[24]
Curcuma longa
H1N1, H6N1
[20]
Dioscoreae rhizoma
SARS
-
COV2
[27]
Emblica officinalis
Influenza Virus
[20]
Ficus religiosa
Human rhino virus
[29]
Galla chinensis
SARS
-
COV2
[30]
Gentianae radix
SARS
-
COV2
[27]
Glycine max
Human adenovirus
[31]
Glycyrrhiza glabra
Respiratory Syncytial virus
[20]
Glycyrrhiza glabra
Herpes type 1 and 2 viruses
[32]
Glycyrrhiza glabra
SARS
-
COV2
[33]
Guazuma ulmifolia Lam
Polio virus
[34]
Hippophae rhamnoides
Dengue virus
[35]
Isatis indigotica
SARS
-
COV2
[36]
Juniperus oxycedrus
SARS
-
COV2
[37]
Laurus nobilis
SARS
-
COV2
[
37]
Linum usitatissimum
SARS
-
COV2
[38]
Loranthi ramus
SARS
-
COV2
[27]
Mangrove plant
HIV
[39]
Moringa oleifera
HIV
[40]
Moringa oleifera
Epstein bar virus
[41]
Myrica faya
SARS
-
COV2
[42]
Nicotiana tabacum
SARS
-
COV2
[43]
Nigella sativa
SARS
-
C
OV2
[44]
Nilavembu kudineer
Chikungunya virus
[31]
Paulownia tomentosa
SARS
-
COV2
[45]
Phyllanthus amarus
Human immuno deficiency virus
[46]
Phyllanthus amarus
Human Immunodeficiency Virus
[20]
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Phyllanthus amarus
Hepatitis B
[47]
Phyllanthus urinaria
Herpes Simplex Virus
[20]
Psoralea corylifolia
SARS
-
COV2
[48]
Pterocarpus santalinus
SARS
-
COV2
[24]
Rheum officinale
SARS
-
COV2
[49]
Rheum palmatum
SARS
-
COV2
[50]
Rhodiola kirilowii
SARS
-
COV2
[51]
Salvia miltiorrhiza
SARS
-
COV2
[19]
Scutellaria baicalensis
SARS
-
COV2
[52]
Scutellaria lateriflora
SARS
-
COV2
[42]
Sesbania grandiflora
Herpes simplex virus
[53]
Stephania cepharantha
SARS
-
COV2
[54]
T. nucifera
SARS
-
COV2
[55]
Terminalia belerica
HIV
-
1
[56]
Terminalia bellerica
HIV
-
1
[5
7]
Thuja orientalis
SARS
-
COV2
[37]
Tinospora cordifolia
Human Immunodeficiency Virus
[20]
Toona sinensis
SARS
-
COV2
[27]
Triterygium regelii
SARS
-
COV2
[55]
Utrica dioica
SARS
-
COV2
[58]
Veronica linariifolia
SARS
-
COV2
[51]
Withania somnifera
He
rpes Simplex Virus 2
[20]
In Brazil, Acmella oleracea is a well-known herb that belongs to the asteraceae family. It is
used for the local ‘Jambu tea’ preparation consumed daily in every home in Brazil. This plant
contains a lot of phytomolecules, among which Spilanthol, undeca-2,7,9-trienoic acid isobutyl
amide, and undeca-2-en-8,10-diynoic acid isobutyl amide are well known. It has been proved that
the extract of this plant has anti-microbial properties [72].
Ocimum sanctum, Acacia nilotica, Ocimum kilimandscharicum, Euphorbia granulate, Eugenia
jambolana, Solanum nigrum, and Vitex negundo inhibited HIV and Sambucus ebulus reversed
transcriptase activity inhibiting enveloped virus activity [73–79]. All these plants may be applicable
as the effective agents against SARS-CoV-2.
Cinnamomum camphora (Camphor): In India, herbal product camphor is commonly used as a
white crystalline substance derived from camphor laurel wood (Cinnamomum camphora), a tree
belongs to the lauraceae family. Camphor is obtained by distilling steam, purifying, and sublimating
wood [80]. This is distributed in India, Taiwan, Japan, China, Mangolia, and especially in Florida.
This product has a very fine history as the antispasmodic, odontalgic, anti-rheumatic, and
rubifacient medication. The Chinese oil for sassafros obtained from C. Camphora. The camphor is
composed of camphor, sofrole, linalool, borneol, dipentene, terpeneol, and cineole [81]. It is also
well established that Camphors has antihistaminic activity, antibacterial activity, anti-inflammatory
activity, bronchitis antioxidant activity, sprain, rheumatic pain, etc., immunoglobulin-E suppressing
allergic disease activity [82]. A characteristic organized feature of camphor molecule is its rigid
structure of cage-hydrocarbons such as amantadine, rimantadine, most potent antiviral drugs [83].
These compounds' antiviral activity is due to the blockage of virally encoded protein-M2, which acts
as a protein channel necessary for the hemmagglutinin cleavage and adhesion of host cell
membranes and viral envelope [84]. New biologically active antiviral compounds are obtained by
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chemical modification of the natural compounds that occur. The camphecene (Fig. 1) is a recent
camphor amino derivative, with high antiviral activity and low toxicity [85]. The camphecene is
based on hepten-2-ylidene-aminoethanol-1,7,7-trimethylbicyclo(2.2.1); Amino camphor derivatives
are an important influenza A inhibitor of M2 ion channels (viral haemagglutinin) [86]. Bananins are
potent antiviral compounds close to classical adamantanes (trioxa-admantene moiety covalently
linked to pyridoxal derivatives). Tanner et al. [87] reported that bananin and its derivatives are
potent inhibitors of both SARS-Coronavirus ATPase and helicase activities, thus inhibiting the
replication of SCVs. In Iran, triggered by the use of homeopathic medication Camphor-1 M,
COVID-19 related deaths dramatically reduced. In India, the ministry of Ayurveda, Yoga &
Naturopathy, Unani, Siddha and Homoeopathy (AYUSH) has recommended the use of Arsenicum
Album 30 (Ars Alb 30C) and Camphor 1 m (homeopathic formulations) in COVID-19 under
physician supervision for prophylaxis usage. Thus, these drugs were issued to several Indian states
and police forces.
Ocimum sanctum (Tulasi): Because of its medicinal and spiritual values, Tulasi (Ocimum
sanctum) belongs to the plant family Lamiaceaeis widely used in the Indian medicinal system; also
known as holy basil, Mother Natural Medicine, and "The Queen of Herbs" This is found in the
Himalayas in all of India climbing up to 1800 m. Tulasi's main bioactive molecules are oleanolic
acid, rosmarinic acid ursolic acid, carvacrol, eugenol, and caryophyllene. There are hundreds of
scientific studies showing that this plant has a special combination of behavior including anti-
diarrheal, anti-oxidant, antimicrobial (including antifungal, anthelmintic, antibacterial, antiviral,
antimalarial, antiprotozoal), hepato-protective, anti-inflammatory, neuroprotective, antidiabetic,
cardioprotective, analgesic, anti-allergic, antipyretic, immunomodulatory, cardioprotective, and
anti-inflammatory. Extract from Ocimum sanctum has considerable potential to inhibit the produced
free radicals in the cell. There was strong antioxidant activity in the phenolic compounds, i.e.,
apigenin and rosmarinic acid, isothymusin, cirsimaritin, cirsilineol, and large amounts of eugenol
from stems and leaves [77]. Ocimum sanctum demonstrates its immunomodulatory effect by
increasing the number of IL-‘4, NK cells, IFN-γ, T-helper cells. This helps to reduce the increasing
population of neutrophils, and lymphocytes and thereby increasing phagocytic activity and
phagocytic index. In bovine sub-clinical mastitis, the aqueous extract also exhibited
immunotherapeutic potential by inhibiting mast cell degranulation and histamine release in the
presence of an allergen. This is more effective for treating acute viral encephalitis than
dexamethasone [88]. Since the 1990s, the flavonoid molecules (6-hydroxyflavone, Apigenine (Fig.
1), tangeritin, wogonin, scutellarein, chrysin, and luteoline) of the plant extract has increased
antiviral effect in cell culture on herpes simplex virus types 1 and 2 [89]. Pandey et al. [90] reported
naturally extracted flavonoids have the evidence to inhibit the helicase activity of SARS-CoV due to
suppression of ATPase activity.
Zingiber officinale (Ginger): Zingiber officinale (Ginger) belongs to the Zingiberaceae family and
is among the most commonly used herbs. The Rhizome is the eaten portion of the ginger. It has
been developed as a spice for a long time. From the last decade, it is being used as a traditional
medicine in the different medicinal system [91]. Ginger includes various substances, such as
gingerol, gingerdiol, and gingerdione, which have anti-inflammatory, anti-diabetic, anti-cancer,
chemopreventive and chemotherapeutic effects, anti-microbial and anti-oxidant properties of ginger
[92–94].
Tinospora cordifolia (Giloy): Tinospora cordifolia is commonly known as Giloy or Guduchi.
Three major species of Tinospora viz., Tinospora candifolia, Tinospora malabarica, and Tinospora
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crispa are found primarily in Myanmar, mainly tropical and subtropical regions of India, Sri
Lanka, and China [95]. Flavonoids, glycosides, phytosterols, alkaloids, polysaccharides, and others
are the active constituents of the plants. Several chemical components, such as giloin, tinosporic
acid, tinosporite, berberine, palmatin, isocolumbin, columbin, choline, tinochordifolin, and others
were extracted from the various parts of tinospora [95]. This plant is also recognized for anti-allergic,
anti-oxidant, anti-inflammatory, anti-pyretic, anti-oxidant, anti-spasmodic, and anti-cancer
properties [96]. Tinospora is a potent natural immunomodulator. It induces chemotaxis,
phagocytosis of macrophages, and activates B- lymphocytes and other immune controlling cells [97].
Giloy root extracts have shown positive modulation of the immune system in HIV patients. It was
reported that T. Chordifolia has a protective effect against swine flu [96]. T. Chordifolia has a high
potential for anti-stress and antioxidant [98]. Giloy's phytochemicals such as tinocodiside could be
potent against COVID-19. Exactly within the ACE2-RBD complex, in-silico model tinocodisides
dock has been found which suggests that rich giloy extracts of Tinochordiside may be the best
options to inhibit the host cell entry of COVID-19. Giloy’s immunomodulatory property will
strengthen innate immunity to COVID-19 infections [99].
Glycyrrhiza glabra (Mulethi): Several in vivo and in vitro studies reported that Licorice and
glycyrrhizine have the potential as the therapeutic agent against several viral diseases including
vaccina virus, chronic hepatitis A, B and C, respiratory syncytial virus, human immunodeficiency
(HIV) virus, SARS-related coronavirus, arboviruses, and vesicular stomatitis virus (VSV) [100–103].
Nyctanthes arbortristis (Tree of sorrow or Harsingar): Nyctanthes arbortristis also known as
Harsingar or Parijatha belongs to the family of Oleaceae/Nyctanthaceae. Leaves from the N.
Arbortristis contains oleanolic acid, methyl salicylate, astragalin, iridoid glycosides, amorphous resin,
flavanol glycosides, nicotiflorin, a trace of volatile oil, carotene, β-sitosterol, benzoic acid, and
nyctanthic acid. Nyctanthes arbortristis seeds contain Arbortristoside A&B, oleic acid, glycerides,
lignoceric acid, linoleic acid, and 3-4 secotriterpene acid. The bark of N. Arbortristis contains both
glycosides and alkaloids [104]. The bronchodilatory effect of this plant ethanolic extract was
demonstrated in in-vitro circumstances [105]. Stabilizing mast cell and bronchodilating activity of N.
Arbortristis bark has been shown to treat asthma [106]. Administration of doses of 0.25 and 0.5 g/kg
body weight of plant ethanolic extract found that there was a significant increase in splenic antibody-
secreting cells, leukocyte count, phagocytic index [107]. Plant ethanolic extract along with
arbortristoside C and arbortristoside A; have inhibitory activity against Semliki Forest Virus (SFV)
and encephalomyocarditis virus (EMCV). The in-vivo ethanol extract of N. Arbortristis and n-butanol
fraction protected EMCV infected mice against SFV [108].
Camellia sinensis (Herbal Tea): Tea leaves (Camellia sinensis) are rich in polyphenol (catechins
and flavonoids) [109]. Green tea contains six primary catechin compounds such as epigallocatechin,
epicatechin, epicatechingalate, catechin, gallocatechin, and epigallocatechin gallate (Fig.
1).Polyphenols vary from 30% to 40% and from 3% to 10%, respectively in green tea and black tea.
The health benefits of tea consumption are well known and widely reported in the literature [110].
There has recently been hype concerning the usefulness of tea in the treatment of COVID-19.
Preliminary evidence in the past has suggested that tea components could be a potential antiviral
agent that could potentially inhibit coronavirus (COVID-19) proliferationin the human body [111].
This led to the assumption that the consumption of tea could be beneficial against SARS Cov-2 due
to its abundant chemical constituents. Polyphenolic compounds like Prodelphinidine B-2 39-gallate
inhibited the entry of HSV type 2, HIV-1 into target cells. ECGC has also been reported to prevent
influenza virus infection by binding to viral hemagglutinin [112]. Catechins have anti-influenza virus
activity [75]. Epigallocatechin gallate has a higher activity than the epicatechingalate activity against
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viral infection after suppressing the viral DNA and RNA polymerases. However, the strongest
inhibition of these compounds was observed with HIV reverse transcriptase [113,114].
Epigallocatechin gallate has reported blocking the binding of HIV-1 glycoprotein 120 to CD4
molecules on T-cells [115].
Withania somnifera (Ashwagandha): Withania somnifera, a family shrub of Solanaceae, is
generally used as an immunosuppressive agent in folk medicines. Its medicinal properties have been
attributed to its major bioactive constituent steroidal lactones called anolides. This is oxygenated
steroidal molecules. About 130 anolides have been isolated from Withania sp. and they are well
established for the anti-inflammatory, anti-tumor, antioxidant, and anti-microbial properties have
been demonstrated. Infectious Bursal Disease Virus Replication was stunned after the application of
hydro-alcoholic extract of W. Somnifera [116].
Antiviral Herbs as Potential Anti-COVID Agent: The unsung Himalayan floral diversity is
known as the storage house of the medicinal plants [62]. From ancient times, the ethnomedicinal
properties of the available plats were known. Recently, numerous plants found in this region have
reported that they have the properties as anti-SARSCoV-2, anti-influenza virus infections, and other
anti-viral infections [59,60,117,118]. The extract of these plants mainly inhibits the virus entry to the
cell, inhibition of viral replication, inhibiting the NF-kB pathway, immunomodulation in the host
cell, etc [60,66]. The herb lemongrass is known as Cymbopogon sp., mainly found in Asian and
African countries, and commonly found in Australia. Lemongrass extracted essential oil (EO) has
great potential as an antimicrobial agent. Studies have shown that lemongrass EO affects the
antimicrobial resistance of pathogens [119,120]. Other studies also reported an extract of
Cymbopogon sp. possible antiviral activity. Bahtiar et al. [121] reported that the ethanol extract of
Cymbopogon nardus attenuated the activity of herpes simplex virus serotype 1 (HSV-1), anti-measles
activity, anti-dengue virus serotype 1, anti-hepatitis-A virus, anti norovirus murine [122–125].
Antiviral phytochemicals: Phytochemicals provide eco-friendly and substantially applicable in
the public health sector as anti-viral agents. Several pure individual bioactive chemical constituents
from different plants have been investigated for their antiviral activity, with a particular focus on
anti-COVID action. The reported antiviral and anti-COVID activity of various phytochemicals are
summarized in Table 3 and Fig. 14. Curcumin is well known bioactive pigment present in Curcuma
longa (. It is well established the curcumin anti-inflammatory, anti-viral, antioxidant, and anti-cancer,
anti-bacterial properties. This has the inhibitory effects of the HIV replication process in the host cell,
inhibiting HIV kinase-related enzymes, inhibition of several cell signaling mechanisms, etc. [169].
Withaferin A and Withanone (Fig. 1) are the main phytochemical of Withania somnifera; a well-
known medicinal plant. These molecules have the capabilities to reduce H1N1 influenza
neuraminidase activity, inhibiting the effect of viral DNA polymerase activity, reduce the bonding
between the viral RBD and host ACE2 receptor [170]. Therefore, these molecules may reduce the
infective power of COVID-19 [99] Caffeine, theobromine, and theophylline (Fig. 1) are the main
bioactive molecules in the tea leaf. Theaflavins-1, Theaflavins-2, and Theaflavins-3 (Fig. 1) are also
present in the black tea and they are now known for the SARS-COV-2 viral replication process in the
host cell [111]. Artemisinin (ART), dihydroartemisinin (DHA), and artesunate (AS) (Fig. 1) are the
active ingredients derived from Artemisia annua. For a very long time, this is used in Chinese
traditional medicine [75]. These molecules reported their antiviral effect in the fibroblast cell model
by measuring viral DNA synthesis in cell lysates, antimalarial, anti-bovine viral diarrhea virus
(BVDV) [171,172]. Artemether is often used alongside lumefantrin. One clinical version of this
formulation is Coartem®. The combination of artemether-lumefantrine has also been used in
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patients diagnosed with EBOV and has shown a decreased efficacy in reducing the risk of death
[173]. The study of Arisaema tortuosum plants found that the extract of this plant has a proven
mechanism for attenuating the HSV-2 replicative cycle. Apigenin and luteolin had high inhibitory
activity against the HSV-2 replicative cycle [174]. Phytomolecules such as isorhapontigenin,
gnetupendin B, shegansu B, and gnetin D have significant anti-influenza viral activity in the in vitro
condition [175]. The use of icetexane diterpenoids, namely perovskatones B–D, α-
hydroxybrussonol, and α-hydroxypisiferanol (Fig. 1); isolated from Perovskia atriplicifolia, has been
used against inhibitory hepatitis B virus activity in the HepG 2.2.15 cell line. The results suggest that
phytomolecules have inhibitory activity against in vitro hepatitis B virus activity [176]). The root of
the Marsdenia tenacissima plant was used for the extraction process and marstenacissides B10–B17,
marstenacissides A8-A12, polyoxypregnane glycosidesmarsdenosides M, and L,
isolatedmarstenacissides A1–A7 and B1–B9 (Fig. 1) were isolated and identified. The anti-HIV
activity was reported [177]. Naphthoquinone droserone is a natural product found in dicotyledonous
plants. Lieberherr et al. [178] have shown that this molecule has great potential for entry into cells of
the measles virus.
Table 3 Bioactive phytochemicals with virus inhibiting action
Bioactive compounds Source Plants Virus inhibiting action References
1, 8-cineole Vitex trifolia Inhibition of SARS-CoV-2 virus [126]
10-Methoxycamptothecin Camptotheca acuminata Inhibit adenovirus, Herpes and
vaccinia viruses
[127]
6
-
deoxyglucose
-
diphyllin
Justicia gendarussa
Inhibition of Zika Virus, Human
Immunodeficiency Virus
-
1
[128]
6-gingerol Zingiber officinalis Anti-viral action against Avian influenza
virus H9N2
[129]
7′R,8′S,7″R,8″S)-
Erythrostrebluslignanol G
Streblus asper Lour.,Moraceae Inhibition of Hepatitis B [130]
Actinophnine Actinodaphne hookeri Herpes simplex virus type 1↓ [131]
Aranotin, Gliotoxin Arachniotus aureus Coxsackievirus A 21, poliovirus, rhinovirus,
influenza virus, para-influenza virus type 3↓
[132,133]
Azadirachtin
Azadirachta indica
Virucidal activity against FMDV
[50]
Bicyclol
Schisandra rubriflora
Inhibition of Hepatitis B, Hepatitis C
[134]
Buchapine
Euodia roxburghiana
HIV-1-reverse transcriptase
↓
[135]
Camptothecin
Ophiorrhiza mungo
s
Herpes virus
↓
[136]
Canavanin Carnavalia ensiformis L. Influenza virus, Semliki Forest virus ↓ [137]
Caribine Hymenocallis arencola Antiviral activity [138]
Carinatine
Zephyranthes carinata
Antiviral activity
[138]
Carnosic acid Rosmarinus officinalis Blocks replication of Human
Respiratory syncytial virus
(hRSV)
[139]
Castanospermine, Australine Castanospermum australe HIV↓ [140]
Chelidonine Chelidonium majus L.
Herpes virus, influenza virus
↓
[138]
Cordycepin Cordyceps militaris Picornavirus, poliovirus, vaccinia, Newcastle
disease virus, Herpes simplex, and influenza
viruses
↓
[141]
Cryptopleurine Bochneria cylindrica L. Sw. &
Cryptocarya
pleurosperma
Herpes simplex type 1 ↓ [142]
Diphyllin Justicia gendarussa Inhibition of Zika Virus [143]
Ellagic acid, Isoquercetin,
Kaemferol
Eugenia jambolana Inhibition of protease activity in Avian
Influenza
[66]
Emetine Cephaelis ipecacuanha A MERS, SARS [144]
Fagaronine
Fagara zanthoxyloides
Lam
Reverse transcriptase activity of retrovirus ↓ [145]
Flavonoids and Alkaloids Hyoscyamus niger Inhibition of Ca
2+
channels and
Bronchodilator SARS
-
CoV
-
2
[146]
Flavonol glycosides Clitoria ternatea Inactivation of SARS-CoV-2 [147]
Glaucine fumarate, N-
Methyllaurotetanine, Isoboldine,
Herpes simplex virus Corydalis cava, Glaucium flavum, Peumus boldo↓
[148]
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Nuciferine HCl
Glycyrrhizin
Glycyrrhiza glabra
Induces nitrous oxide synthase which in turn
blocks replication of SARS-CoV
[30]
Harmaline, Harmine
Peganum harmala
DNA-containing herpes virus type 1 (HSV-1)
↓
[149]
Harmine Peganum harmala Inhibit replication of Influenza Avirus [33]
Hinonkin Chamaecyparis obtusa Inhibition of Human Cytomegalo Virus,
SARS
‑
CoV
[24]
Hypoxanthine Beta vulgaris Viral diseases
↓
[150]
Luteolin Reseda luteola Inhibit entry of SARS-CoV, have great
affinity for S2 protein thus interfere virus-cell
fusion process in SARS-CoV
[151]
Menthol and
essential oils
Mentha piperita Virucidal impact on IBV by incrementing
virion density
[152]
Nordihydroguaiaretic acid Larrea tridentata
Inhibition of Hepatitis C virus, West Nile
virus, Zika virus
[153]
Ochropamine, epi-16-
Ochropamine
Cabucula erythrocarpa
Vatke Mar
Influenza virus ↓ [154]
O
-Demethyl-buchenavianine Buchenavia capitata Cytopathic effect of HIV
↓
[155]
Odorinol
Aglaia roxburghiana
Ranikhet disease virus
↓
[156]
Oleanane triterpenes Camellia japonica Block replication of PEDV-CoV via affecting
key structural protein synthesis
[157]
Oliverine Polyathia oliveri Herpes simplex virus type 1
↓
[131]
Oxostephanine Stephania japonica Herpes simplex virus type 1
↓
[131]
Pachystaudine
Pachypodanthium staudti
Herpes simplex virus type 1
↓
[131]
Papaverine
Papaver somniferum
Cytomegalovirus (CMV), measles and HIV
↓
[154]
Phenolics Acacia nilotica Inhibition of HIV-PR [158]
Phytosterols and
Phenolics
Strobilanthes callosa Blocking of HCoV-NL63 virus [69]
Platycodin D Platycodon
grandiflorum
Inhibit viral replication and proinflammatory
cytokine expression in PRRSV
[159]
Polyphenols Rheum palmatum Significant inhibition of protease activity
SARS
-
3CL
[160]
Psychotrine
Cephaelis acuminata
HIV
-
1
↓
[135]
Punicalagins and
Ellagitannin
Punica granatum Inhibition of ACE SARS-CoV-2 [161]
Quercetin Houttuynia cordata Virucidal activity against MHV, DENV-2,
inhibits ATPase of multidrug resistance-
protein
[162]
Quercetin and kaempferol
Moringa oleifera
Blocks initial stages of replication of FMDV
[163]
Quinazolinone, alkaloids and
monoterpenes
Strobilanthes cusia Blocking of replication of HCoV-NL63 virus
[69]
Resveratrol
Vitis vinifera
Reduced expression of nucleocapsid (N)
protein, also lowers the apoptosis induced by
MERS-CoV virus
[164]
Rifampin
Streptomyces mediterranei
Vacc
inia, pox viruses
↓
[53]
Schumannificine Schumanniophyton
magnificum
HIV and anti- Herpes simplex (anti-HSV) ↓ [155]
Solasonine Solanum nigrum & S. khasianum Tobacco mosaic virus and sunnhemp
rosette virus
↓
[165]
Taspine Croton lechleri M. RNA-directed DNA polymerase activity of
avian myeloblastosis virus ↓
[154]
tetra-O-
methylnordihydroguaiaretic
acid
Larrea tridentata
Inhibition of Herpes Simplex Virus, Human
Influenza Virus
[166,167]
Yatein Chamaecyparis obtusa Inhibition of Herpes Simplex Virus 1 [168]
Nocchi et al. [179] found that Schinus terebinthifolia plant’s bark extract reduces infections of
the Herpes simplex virus in cells.
CONCLUSION
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Currently, effective treatments against Covid-19 are unavailable. There may or may not be
one in the near future. In such circumstances, medications commonly used for other viral infections
such as Malaria, Ebola Virus Disease (EVD), Severe Acute Respiratory Syndrome (Sars-CoV),
Middle East coronavirus-related respiratory syndrome (MERS-CoV) are considered
(repurposing/repositioning) as therapeutic options. Every medical specialty around the world claims
they have some help available to either prevent, treat, or cure potential infectious viral pathogens.
This includes, but is not limited to, Siddha, Ayurveda, Unani, Complementary and alternative
medicine (CAM) therapies, natural and indigenous tribal medicine. Several communities eschew
drugs for Covid-19 but resort to natural medicine as it is believed that the home-made remedies are
much safe without mush side-effects, and additionally have great preventive curing capabilities. For
example, native South American from Amazonia uses ‘toothache plant’ (Acmella oleracea) to prepare
an herbal tea (jambú tea) home remedy. Traditional herbal remedies from India and other countries
and Traditional Chinese Medicine (TCM) are currently being explored. In India, the Ministry of
Ayurveda, Yoga & Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) has been involved in
the research and dissemination of indigenous alternative medicine systems. However, the aim was to
promote traditional healing therapies and to list various practices that prevent infectious agents from
occurring, strengthen the immune system, thereby improving the overall health and well-being of the
individual, but not promoting it as a primary treatment.When patients and consumers resort to any
of these alternative supportive therapies, care must be taken to avoid potential side effects. The
World Health Organization (WHO) has released a general warning against the use of unproven
treatment. Besides, there are many fraudulent claims concerning prevention, cure, and management
for COVID-19. Hence, patients and consumers are advised to consult appropriate medical specialties
and avoid self-diagnosis and treatment or while using over-the-counter preparations.
ACKNOWLEDGMENTS
The authors are indebted to the anonymous reviewers for providing insightful comments on
earlier drafts of the manuscript and directions for additional analysis to improve the quality of the
paper. Without the anonymous reviewers, supportive work this paper would not have been possible.
Ethical approval and Compliance with ethical standards. This article does not contain any studies
with human or animal subjects performed by any of the authors. Hence, no ethical approval was
needed for this work. No primary data have been reported in this study.
CONFLICTS OF INTERESTS
The authors have read the journal’s policy and have the following potential conflicts: This
study was not industry-supported. S.R. Pandi-Perumal is a stockholder and the President and Chief
Executive Officer of Somnogen Canada Inc., a Canadian Corporation. This does not alter his
adherence to all of the journal policies. Pandi-Perumal has edited several academic volumes for
which he receives occasional annual royalties. He declares that he has no competing interests that
might be perceived to influence the content of this article.
Other remaining authors declare that they have no proprietary, financial, professional, nor
any other personal interest of any nature or kind in any product or services and/or company that
could be construed or considered to be a potential conflict of interest that might have influenced the
views expressed in this manuscript.
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The views expressed in this article are those of the authors and do not necessarily represent
the official views of their affiliated institutions.
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