10. Rheum palmatum L.

This herbal plant belongs to the family of Polygonaceae. It is mostly found in mountainous regions
with high elevations, such as the Sichuan, Gansu and Shaanxi regions of China [81]. It is effectively
used as a laxative or astringent for the treatment of stomachache, hemorrhoids, liver bile disease
or gastroenteritis [243]. It contains some potent bioactive compounds including emodin, physcion,
chrysophanol, rhein and aloe-emodin [80,82]. Known biological activities are antiviral, anti-pyretic,
anti-neoplastic, anti-spasmolytic, antibacterial, laxative, hemostatic and anti-spasmodic [79,81,82,244].
It was also used against SARS-CoV-1 infection, due to its potential efficacy for acting on the ACE-2
receptor, leading to blockage of viral entry into cells and replication of the CoVs [78,80]. An in vitro
study conducted by Ho et al. 2007 showed the potential of Radix et Rhizoma Rhei (root tubers of Rheum
palmatum L.) in blocking the entry of SARS-CoV-1 to inhibition sites such as the ACE-2 receptor [78].
Furthermore, the major active component of this plant is emodin, which is responsible for blocking the
binding of SARS-CoV-1 S protein to ACE-2 receptor [78,80]. Therefore, the use of emodin extracted
from Radix et Rhizoma Rhei can be considered for the possible therapeutic management of COVID-19.
This will possibly provide us with new insight into therapy against SARS-CoV-2.

11. Polygonum multiflorum Thunb.

Polygonum mulitflorum Thunb (PMT) is mostly found in China, Korea and Japan, belonging
to Polygonaceae family [245]. Radix Polygoni multiflori (root tubers of PMT) is mostly used
in treating many kinds of diseases, such as rubella, scrofula, waist and knee pain, paralysis,
vaginal discharge, hypercholesterolemia (liver and kidney), malaria, and various other diseases,
possessing neuro-protective, antioxidation, immunomodulation, anti-hyperlipidemia, anticancer,
heap-toprotection, anti-inflammation, and anti-CoV functions [86,87,246]. The potent bioactive
compounds present in PMT which are responsible for the therapeutic effects against various diseases
are listed in Table 1 [84,85,88,247]. However, Ho et al. found that emodin is the most effective
compound against SARS-CoV-1. The data were published to show the potential and efficacy of PMT in
blocking the entry of SARS-CoV-1 by acting on the ACE-2 receptor [78]. The mode of action of PMT is
similar to Rheum palmatum L and the major active constituent is found to be emodin in both plants.
Therefore, it is highly recommended to focus on emodin for possible and effective management of
SARS-CoV-2 infection, combination with other therapeutic approaches.

12. Cerasus avium (L.) Moench.

This Persian medicinal plant belongs to the Rosaceae family and is mostly used as an antioxidant,
antimicrobial and antiviral [93]. Its stem contains polyphenols, carotenoids, vitamins, minerals and
many other bioactive components [90,248]. However, this plant has strong potential to act on the
ACE-2 receptor and block the further processing of the viruses [78,92,94]. According to Ziai et al.’s
2009 in vitro study, this plant showed very good potential to inhibit or completely block the ACE-2
receptor [94]. Subsequently, Heidary et al., 2020 recently suggested that this plant has good potency
against SARS-CoV-2 and must be used for the treatment of its infection [91].

13.  Alcea digitata (Boiss.) Alef.

Alcea digitata (A. digitate) is a Persian medicinal plant belonging to the Malvaceae family
with antiviral, antioxidant, anti-inflammatory, antimicrobial, anti-tussive, expectorant and laxative
therapeutic effects [96,97]. The flowers of A. digitata have been used for lung and respiratory
disorders, head and neck cancer, and lubrication of the throat [97]. According to one published
report [96], A. digitata is known to have good potential to block or inhibit the ACE-2 receptor. Recently,
Heidary et al., 2020 suggested that A. digitata can possibly show good inhibitory effects against
SARS-CoV-2 infection [91].

14. Citrus aurantium L.

Citrus aurantium (C. aurantium) belongs to the family of Rutaceae and is generally known as
bitter orange [249]. This plant is known to have many essential components with biological
effects [100,101], such as phenolics (flavanone glycosides, hydroxycinnamic acids), vitamin C,
and carotenoids [99,249,250]. However, C. aurantium fruit extract is manly used for the treatment
of anxiety, lung related diseases, obesity, gastrointestinal disorders and prostate cancer [249,251], buts
has potential to inhibit or block the ACE-2 receptor. Some in vitro studies have shown its efficacy in
inhibiting ACE-2 receptors [91].

15. Rubia tinctorum L.
Rubia tinctorum (R. tinctorum) is mostly found in Southern Europe, Western Asia and North Africa
and belongs to the family of Rubiaceae [252]. R. tinctorum is mostly used to treat kidney and bladder
stones, and menstrual and urinary disorders [104,253]. Furthermore, the root of R. tinctorum contains
red color due to the presence of anthraquinone, alizarin and pseudopurpurin, which is also used
for dyeing purposes [103]. On the other hand, R. tinctorum has shown potential to inhibit or block
the ACE-2 receptor [91]. in vitro studies revealed the efficient use of R. tinctorum to inhibit ACE-2
receptors [91].

16. Allium sativum L.
The common name of Allium sativum (A. sativum) is garlic, and it belongs to the Amaryllidaceae
family. A. sativum use for human welfare has been reported for thousands of years in the
form of a spice [108]. It is an aromatic herbaceous plant and is consumed worldwide as a
food as well as a remedy for different diseases [108]. A. sativum is reported to have numerous
biological properties, such as antibacterial, antifungal, anti-carcinogenic, antioxidant, anti-diabetic,
reno-protective, anti-atherosclerotic, and anti-hypertensive effects. Cloves of this traditional
medicinal plant contain several potent components, such as alliin, allicin, ajoenes, vinyldithiins,
and flavonoids [108,109,254–256], due to which it is mostly used for treatment of various
disorders [106–109,257]. On the other hand, an in vitro study conducted by Ziai et al., 2009 on
A. sativum and its potential efficacy to inhibit the ACE-2 receptor reported some effective results [94].

17. Quercus infectoria G. Olivier.
Quercus infectoria (Q. infectoria) is commonly known as gall oak and belongs to the family of
Fagaceae [112]. This medicinal plant is traditionally used for the treatment of diarrhea, menorrhagia,
dysentery, gonorrhea, tonsillitis, impetigo and internal hemorrhages [112,258]. Bioactive constituents
of Q. infectoria gall extract include phenolic compounds (catechol, p-hydroxybenzoic acid, caffeine,
catechin, pyrogallol, e-vanillic acid, 3-hydroxytyrosol cinnamic, p-coumaric, gallic acids and resveratrol),
flavonoids (naringin, rutin, 7-hydrohyflavone and hispertin) [111,259,260] with biological activities
such as antiviral, antifungal, antibacterial, antioxidant, anti-inflammatory, anti-diabetic, anti-parasitic,
anti-venom, etc. [112,114,261]. Q. infectoria has also shown strong potential to completely block the
ACE-2 receptors due to the presence of many potent and tannin active components in vitro [113].
Similarly, this medicinal plant can also be considered for combinational therapeutic approaches in
controlling the COVID-19 pandemic directly or indirectly.

18. Onopordum acanthium L.
Onopordum acanthium (O. acanthium) basically belongs to a family of Asteraceae and is commonly
known as Scotch thistle [118]. It is found all over the world [262]. The biological activities of O. acanthium
include antiviral, anti-tumor, anti-inflammatory and antioxidant effects. Extracts from the leaf, flower,
stem and root of O. acanthium are also used as cardiotonic agents. O. acanthium contains many bioactive
components, such as flavonoids, triterpenoids, lignans, phenylpropanoids, sesquiterpene lactones,
and sterols [116,117,262]. Moreover, O. acanthium has shown efficacy to completely inhibit the activity
of ACE-2 due to the presence of tannin bioactive components, as demonstrated by Sharifi et al., 2013 in
his in vitro study. This makes it a considerable choice to test against SARS-CoV-2.

19. Berberis integerrima Bunge.
Berberis integerrima (B. integerrima) belongs to the family of Berberidaceae, with different parts
of the plant showing different colors [121]. It is mostly found in Iran and contains many types of
alkaloids [122]. Bioactive components extracted from the root of B. integerrima include berbamine,
berberuin, palmatine, oxyacanthine, malic acid, ascorbic acid, caffeic acid, ursolic acid, coumarin,
beta-carotene and tannin [120,122]. B. integerrima possesses many bioactive properties, such as antiviral,
anti-inflammatory, anti-hyperglycemic, anti-hyperlipidemic, anticancer, and antioxidant effects, as well
as being a liver protective agent [120–122]. Moreover, this medicinal plant was tested by Sharifi et al.,
2013 in vitro. His team showed that the usage of a 330 µg/mL concentration of B. integerrima was
able to inhibit the ACE-2 receptor due to 88.2 ± 1.7 IC50 [113]. Therefore, B. integerrima can be further
investigated for its potent medicinal values and may provide fruitful results against SARS-CoV-2.

20. Crataegus microphylla C. Koch
This medicinal plant belongs to the family of Rosaceae and almost all parts of the plant are
used for remedial purposes [126]. It is widely used for the treatment of many diseases, including
heart muscle cells activation, coronary dilation, regulated blood flow, use as an antioxidant and
anti-diabetic, and many others [125,126]. It contains flavonoids (phenols, phenolic acids, procyanidins,
flavonoids, triterpenes, polysaccharides, catecho-lamines) which help in controlling/regulating various
diseases [120,124–126]. Furthermore, it has also showed efficacy to inhibit the ACE-2 receptor and
prohibit the entry of virus into the cell [113]. in vitro results suggested the use of a 330 µg/mL
concentration of Crataegus microphylla was able to inhibit the virus binding to the ACE-2 receptor,
and their IC50 was observed as 80.9 ± 1.3 [113]. The occurrence of some potential bioactive compounds
in this medicinal plant and their efficacy against SARS-CoV-2 must be tested for better drug therapy to
manage COVID-19.

21. Alnus japonica (Thunb.) Steud.
Alnus japonica (A. japonica) belongs to Betulaceae family and originally it was found in Japan,
Korea, China and Russia [128]. This medicinal plant has wide range of biological activities comprising
antiviral, anticancer, anti-inflammatory, and antioxidant effects, as well as the induction of lymphatic
and gastroenteric disorders [128,130]. It is mostly used for the treatment of various diseases such as fever,
cancer, and blood, lymphatic and gastroenteric disorders [263]. Additionally, and most importantly,
A. japonica has been known to have an antiviral effect on SARS-CoV, and its potent bioactive compounds
include hirsutenone, oregonin, rubranoside rubranoside B, rubranol, and hirsutanonol, which are
extracted from the bark of the A. japonica plant [130]. These bioactive components have also been
recommended as a promising medicinal plant for the development of potential drugs against SARS-CoV
PLpro. In 2012, Park et al. investigated the effect and efficacy of A. japonica bark against SARS-CoV.
An in vitro study showed that A. japonica is able to inhibit the SARS-CoV PLpro with IC50 value ranging
21 of 41 from 3 to 44.5 µM of these compounds (hirsutenone, oregonin, rubranoside rubranoside B, rubranol,
and hirsutanonol) [130]. However, the mode of action suggested that A. japonica bark can possibly
inhibit the SARS-CoV PLpro activity.

22. Psoralea corylifolia L.
Psoralea corylifolia (P. corylifolia) belongs to the Leguminosae family and mostly occurs in India,
China, Bangladesh, Indonesia, Malaysia, Sri Lanka and other Asian countries. P. corylifolia is known for
its antiviral, antioxidant, antibacterial and anti-depressant activities [132,133]. Furthermore, it contains
several potent bioactive components such as neoba-vaisoflavone, isobavachalcone, Bavachinin,
40–O-methyl bavachalcone, corylifol A, and psoralidin [264]. In 2014, Kim et al. investigated
the effect of P. corylifolia seed extract and showed an imperative inhibitory effect of SARS-CoV PLpro,
and their IC50 was 15 µg/mL [134]. Furthermore, all these bioactive components were tested by
Kim et al., and the IC50 of these components against SARS-CoV PLpro was estimated to range between
4.2 to 38.4 µM. In addition, psoralidin and isobavachalcone showed the highest inhibitory activity
against SARS-CoV PLpro, with IC50 of 4.2 ± 1.0 µM and 7.3± 0.8 µM, respectively [134].

23. Paulownia tomentosa (Thunb.) Steud.
Paulownia tomentosa (P. tomentosa) is an old Chinese medicinal plant belonging to the Scrophulariaceae
family. It is mostly found in central and western China, Taiwan and Korea. P. tomentosa has wide-ranging
biological activities comprising antiviral, antioxidant and antibacterial effects [136,138]. It is mostly
used for the treatment of various diseases, such as inflammatory bronchitis, upper respiratory
tract infection, asthma, tonsillitis, gonorrhea, traumatic bleeding, enteritis, bacteriological diarrhea,
erysipelas, swelling, bronchopneumonia, conjunctivitis, and hemorrhoids [139,265]. Furthermore,
P. tomentosa has been known to have an antiviral effect on SARS-CoV PLpro. P. tomentosa fruit contains
many bioactive components such as tomentin A, tomentin B, tomentin C, tomentin D, tomentin
E, geranylated flavonones and others [137]. In 2013, Cho et al. examined the effect and efficacy
of P. tomentosa fruit-extracted bioactive components against SARS-CoV. An in vitro study showed
that P. tomentosa is able to inhibit SARS-CoV PLpro activity with an IC50 value ranging from 5.0 to
14.4 µM [137]. Out of all those studied, Tomentin E showed the most promising and highest inhibitory
effect against SARS-CoV, with the lowest IC50 5.0 ± 0.06 µM [137].

24. Tribulus terrestris L.
Tribulus terrestris (T. terrestris) is mostly found in China, India, Pakistan, South Americas, Bulgaria,
Mexico and Spain, and is considered as a traditional medicinal plant. T. terrestris belongs to the
Zygophyllaceae family and possesses several biological activities such as antiviral, anti-inflammatory,
antioxidant, anti-tumor, anti-diabetic and anti-urolithic properties [141,143]. It contains several
bioactive compounds, mainly flavonoids and alkaloids [142,266]. In 2014, Song et al. studied the
effect of T. terrestris fruit extract (six cinnamic amides), and showed significant inhibitory effects
against SARS-CoV PLpro [142]. Furthermore, all bioactive components tested by Song et al. against
SARS-CoV PLpro were estimated to have an IC50 in a range between 15.8 and 70.1 µM [142]. However,
terrestrimine[(E)-N-(1-hydroxy-2-(4-hydroxyphenyl)-2-oxoethyl)-3-(4-hydroxy3-methoxypheny)
acrylamide] showed the utmost inhibitory activity against SARS-CoV PLpro with an IC50 of
15.8 ± 0.6 µM [142].

25. Sambucus nigra L.
This plant belongs to the family of Caprrifoliaceae and is mostly used in the treatment of common
cold, HIV, HSV-1, influenza, urinary tract infection, edema and other rheumatic diseases [149,267].
It contains several active components extracted from the leaves, flower and fruit parts of the plant, such
as flavonoids, lectins, anthocyanin, etc., which have been found to increase the immunity and inhibit
the viral activity [150,152–154]. However, in case of the H1N1 influenza virus, this plant has shown
great potential to block or impede the entry of the virus into the host cells [149,155,268]. Furthermore,
the presence of lectins in this plant is responsible for controlling the symptoms or pathogenesis of
the influenza virus [149,151]. It also has immunomodulating activity due to the presence of peptic
polysaccharides, polyphenolic compounds and flavonoids [149]. Due to several significant and antiviral
relevant properties of this plant, it can possibly be used against SARS-CoV-2.

 26. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim.
Eleutherococcus senticosus (E. senticosus) belongs to the family of Araliaceae and is mostly found in
China, Japan and Korea [269]. E. senticosus is used for the treatment of chronic coughing, ischemic heart
disease, diabetes, cancer, altitude sickness, neurodegenerative disorders, and chronic fatigue [149,159,
269,270]. Moreover, its leaves are used as food in the form of tea, wine, soups and many others [271].
E. senticosus leaves have the potential efficacy to inhibit bacterial glucosidase activity, reported in
in vitro results by many researchers. The nature of the component of E. senticosus responsible for
its antiviral activity remains to be determined, and is currently under investigation together with
the characterization of the target molecules and the molecular basis of the antiviral efficacy of
E. senticosus. However, its extract is able to inhibit the replication of the influenza virus, and viral
replication is common in all kinds of viruses [157–159,272]. Several potent bioactive components
are known to be present in the roots of this medicinal plant, such as phenols, lignans, coumarins,
phenylpropanoids, flavonoids, hyperin, rutin, afzelin, quercetin, kaempferol, phenolic acids, triterpenic
acids, and anthocyanin, etc. Due to the presence of these bioactive compounds, in vitro results showed
some antiviral activity too, by blocking the replication of influenza virus in the cells [149,273]. Therefore,
it is a possible recommendation that plant should go further investigation and may be helpful in
directly or indirectly controlling SARS-CoV-2.

27. Salvia miltiorrhiza Bunge
This plant belongs to the family of Lamiaceae and is commonly known as red sage [274]. Its bioactive
components are extracted from the root, including lipophilic diterpenoids, flavonoids, triterpenoids
and hydrophilic phenolic compounds [163,274,275]. It is also used for the treatment of various diseases,
such as removing blood stasis, improving blood circulation, atherosclerosis, thrombosis, angina
pectoris, other cardiovascular diseases and antiviral activity of HIV-1 and Enterovirus by inhibiting
RdRp enzyme activity [161–164].

28. Acacia arabica (Lam.) Willd.
Acacia arabica (A. arabica) belongs to the family of Fabaceae and is widely distributed
in Asian regions [167]. It is basically used for the treatment of various diseases, such as
Newcastle disease, vaccinia virus, bursal disease virus, H9N2 influenza disease, skin diseases,
and possesses many biological properties including antimicrobial, anti-diabetic, and antioxidant effects.
The mechanism of action of A. arabica is known. It specifically inhibits the stage of viral intracellular
multiplication [149,167–169]. Furthermore, A. arabica contains several bioactive components extracted
from the leaves of the plant which are responsible for its bioactivity, such as flavonoids, methyl 3,4,5
tri hydroxyl benzoate, p-coumaroyl glucoside, p-coumaroylquinic acid, ferulic acid, isoferulic acid,
epicatechin-3-gallate, ascorbic acid, quercetin 3-O-(40-O-acetyl)-rhamnopyranoside, oleic acid, myristic
acid, palmitic acid and steroidal sapogenin aglycone [166–168,276]. A. arabica also has the potential
to inhibit the viral replication against HIV infection [149,169]. Due to its antiviral nature, it is highly
recommended to use A. arabica for controlling/managing SARS-CoV-2 infection.

29. Ocimum sanctum L.
Ocimum sanctum (O. sanctum) belongs to the family of Lamiaceae and is commonly known as
tulsi [167,173]. This aromatic plant is basically found in all Asian countries. It is used for the treatment
of diseases such as cough, anxiety, arthritis, dysentery, diarrhea, asthma, fever, skin and eye disorders,
otalgia, gastrointestinal disorders, cardiac and genitourinary disorders, back pain, snake, insect and
scorpion bites, malaria, and H9N2 influenza disease [16,167,168,173,178]. The leaves of O. sanctum
contain several bioactive compounds, such as alkanoids, saponins, tannins, flavonoids, phenols,
anthocyanins and triterpenoids [167,172,173]. However, this medicinal plant has the potential to
block the activity of different pathogens and can act as a potent antiviral, antifungal, anti-protozoan,
anti-malarial, anti-helminthic, antibacterial, mosquito repellent, etc.; its other clinical activities are
detailed in Table 1 [167,171–177]. Ghoke et al. showed that treatment with the crude extract derived
from the leaves of O. sanctum leads to significant H9N2 virus reduction in assessing all three—virucidal,
therapeutic and prophylactic—activities using an in vivo model. They suggested that the crude extract
of O. sanctum could be a promising extract for developing safe and efficacious antiviral compounds
against the H9N2 virus. The protecting effectiveness of the crude extract of O. sanctum might be
ascribed to multiple mechanisms of action (specific inhibition of viral intracellular multiplication
stage and non-specific interference with virus–cell interactions such as masking/blocking the HA
glycoprotein [167]. Due to these vast known biological properties, it would be of great importance to
study the potential particular active ingredient or combinations, which are responsible for its broader
antiviral activity, further. Therefore, O. sanctum might be helpful for the treatment of COVID-19,
and can potentially block the entry of virus as well as its replication.

30. Ocimum basilicum L.
This medicinal herb belongs to the family of Lamiaceae and it is also known as sweet basil [149,181].
It is mostly used in industries as food, perfumes and cosmetics [181] due to its potent antiviral,
anti-inflammatory, antioxidant and antibacterial activities [180,181,183,184]. Moreover, it contains
several bioactive components such as phenolic compounds, flavonoids and anthocyanin extracted from
the whole plant of O. basilicum [182–184]. This herb has been used for HIV treatment and showed very
good potential to inhibit the replication of the HIV virus, and blocks further viral processing [149,181].

31. Theobroma cacao L.
Theobroma cacao (T. cacao) belongs to the family of Sterculiaceae. The seeds of this cocoa plant are
commonly used in food industries [277]. It contains several types of bioactive compounds, such as
polyphenol, theobromine and flavonoids [278], which are responsible for its antioxidant, antiviral,
anti-inflammatory and many other biological activities [186,188,189]. However, some studies reported
the anti-influenza activity of T. cacao, due to presence of flavonoids, theobromine, lignin, dietary fiber,
free fatty acid, and minerals (zinc, copper, iron) [186–188]. Kamei et al., 2014 investigated the effect of
T. cacao against the influenza virus and found that it enhances the antibody response due to stimulatory
effect [187]. Furthermore, it has also been observed that, T. cacao helps in developing acquired immunity
and activates the NK cells against the influenza virus [187]. Further investigation may lead to the use
of T. cacao against SARS-CoV-2, and can help in boosting immunity.

32. Pelargonium sidoides DC.
Pelargonium sidoides (P. sidoides) belongs to the family of Geraniaceae and is commonly known
as Umckaloabo [191]. It is found all over the world and roots of this plant are traditionally used
for remedial purposes against tuberculosis, respiratory diseases, cough, gastrointestinal infection,
viral diseases and others [191,193]. P. sidoides roots are known to have some potent compounds, such as
methoxycoumarin, proanthocyanidins and prodelphinidins [192]. Furthermore, its roots are also used
for the production of herbal drugs known as EPs 7639 by ethanolic extract, which have been approved
for the treatment of respiratory tract infections [191,194]. According to Theisen et al., 2012, P. sidoides
also has the potential to inhibit the viral entry of the influenza virus [194]. Therefore, it is suggested
that roots of P. sidoides should be further investigated for the treatment of COVID-19.

33. Taraxacum officinale (L.) WEB. ex WIGG.
This medicinal plant belongs to the family of Asteraceae and it is commonly known as dandelion [48].
It is traditionally used for the treatment of various diseases such as kidney diseases, lung diseases,
breast tumor, diabetes, uterus infections, digestive system related abnormalities, etc. [198,279].
Pharmacological research has proven the efficacy of this medicinal plant as antiviral, antibacterial,
choleretic, anti-diabetic, anti-inflammatory, antioxidant, hepato-protective, diuretic and antifungal [198].
It contains several bioactive components, extracted from the aerial parts and roots, such as terpenes,
flavonoids, phenolic compounds, terpenoids, triterpenoids, steroids, coumarins, phenols, saponins,
flavones, flavonols, chalcones, phlobatannins, and cardiac glycosides [196,197,280]. Han et al., 2011
found the potential of this medicinal plant to inhibit the viral replication of HIV [199]. Similarly, Lee et al.,
2012 also suggested its potential to enhance pro-inflammatory cytokines and improve the immune
system [201]. Furthermore, it is also known to inhibit the influenza virus’ entry into cells [48,200].
Therefore, due to its vast and significant antiviral properties, it is highly recommended to conduct
further investigation on this medicinal plant for the discovery of potent drugs against COVID-19.

34. Illicium oligandrum Merr & Chun
Illicium oligandrum (I. oligandrum) belongs to the family of Magnoliaceae, being a rich source of
seco-prezizaane type sesquiterpenes [203]. It is known to have antiviral activity against herpes simplex
virus type 2, coxsackie virus and influenza virus [204,206]. It has some potent bioactive compounds,
such as sesquiterpene lactones, neolignan glycosides, phenolic diglycosides and prenylated compounds
which are responsible for its antiviral activities [204,206]. However, this medicinal plant is also used for
the treatment of rheumatoid arthritis, and neurotoxic and neuro-trophic effects [205]. Ma et al., 2013
reported the ethanolic extraction of spirooliganones A 1 & B from the roots of I. oligandrum and showed
its potential to inhibit the activity of influenza virus (H3N2) (IC50 3.70–33.33 µM) and coxsackie virus
B3 [204].

35. Glycyrrhiza glabra L.
Glycyrrhiza glabra (Liquorice) belongs to the family of Fabaceae and is among the most ancient
medicinal plants [212]. It has several very well-known biological activities, such as antiviral
(HIV, SARS-CoV), anti-inflammatory, antimicrobial, antioxidant, anti-tumorigenic and anti-ulcer
properties [209,210]. The root of Liquorice is known to have many bioactive components, including
flavonoids, glycyrrhizic acid, triterpenoid, saponins, etc. [210,212]. Few studies showed that chalcones
extracted from Liquorice have the ability to block or inhibit the activity of influenza virus [48,208].
Therefore, there is a possibility that this plant might be useful against SARS-CoV-2 due to its
antiviral properties.

36. Angelica keiskei (Miq.) Koidz.
Angelica keiskei (A. keiskei) belongs to the family of Umbelliferae, and its leaves are basically used
for remedial purposes [147]. Its bioactive components include chalcones, flavanones and coumarins,
coumarins phenolic, acetylenes, sesquiterpene, diterpene, and triterpenes [144,146]. A. keiskei is
known and considered to be antiviral, anticancer, anti-inflammatory, anti-obesity, anti-oxidative,
anti-coagulant, anti-tumor, anti-mutagenic, anti-diabetic, antibacterial and hepato-protective [144–146].
Park et al., 2016 extracted bioactive components (9 alkylated chalcones and 4 coumarins) from A. keiskei
plant [146], and revealed that the extracted chalcones were able to significantly block the entry of 
coronavirus (SARS-CoV-1) by inhibiting the chymotrypsin-like protease (75% inhibition using 30 µg/mL
dose) and a papain-like protease (88% inhibition using 30 µg/mL dose) [146]. In addition, the IC50
of this chalcone and chalcone 6 are 11.4 and 1.2 µM, respectively [146]. Therefore, due to this very
specific inhibition property of A. keiskei deserves further investigation for the development of potent
antiviral agents against COVID-19.

37. Polygala karensium Kurz
Polygala karensium (P. karensium) is a medicinal plant belonging to the family of Polygalaceae
and can mostly be found in China, Myanmar, Thailand, and Vietnam [215]. It has important and
potent bioactive compounds, i.e., xanthones, which have shown many biological activities such as
antiviral, antimicrobial, antioxidant, cytotoxicity, etc. [214–216]. In addition, it is also used to treat
various ailments such as cough, bronchitis, neurasthenia, inflammation and amnesia [215]. However,
Dao et al., 2012 conducted one in vitro study on H1N1, H9N2, and novel H1N1 (WT) strains using
ethanol-extracted xanthones from the root of P. karensium, and found that xanthones have the potential to
completely inhibit influenza virus activity [214]. Therefore, xanthones from P. karensium can also be one
of the choices worth investigation for the further development of phytomedicine against SARS-CoV-2.

38. Calophyllum brasiliense Cambess.
Calophyllum brasiliense (C. brasiliense) is a medicinal plant, and basically belongs to the family
of Clusiaceae, mostly found in South America, Central America and the Caribbean region [218].
It is used as a remedy to treat several diseases, such as parasitic, viral, bacterial and fungal
diseases [218,220]. Its potent biological activities include antiviral, antibacterial, anti-protozoal and
antifungal effects [218,219]. However, Kudo et al., 2013 investigated the role of this medicinal plant
in HIV disease, firstly by extracting tricyclic coumarin from the leaves of C. brasiliense and testing
in vitro [220]. Hence, they revealed that tricyclic coumarin from C. Brasiliense possesses great potential
to inhibit viral replication by blocking the NFkB pathway [220].

39. Cimicifuga foetida L.
Cimicifuga foetida (C. foetida) belongs to the family of Ranunculaceae and it is also known as Shengma.
It is abundantly distributed in Asian region [225]. It is basically used to treat various ailments, such as
fever, headache, sore throat, toothache, uterine prolapse and inflammation [224]. It contains several
bioactive compounds extracted from rhizomes, including cycloartane triterpenoids and glycosides
with antiviral, anti-tumor, anti-inflammatory activities [225]. Wang et al., 2012 investigated the role of
C. foetida, especially the cimicifugin component of it, against Respiratory Syncytial Virus, and found
that the plant has a strong potential to inhibit viral attachment and internalization [223,224]. Moreover,
cimicifugin was also able to stimulate epithelial cells and initiate the secretion of cytokines such
as IFN-β, to clear the viral infection/load [281]. Furthermore, another in vitro study conducted by
Dai et al., 2016 observed the potential of C. foetida in inhibiting the hepatitis B virus transcription
and replication by producing pro-inflammatory cytokines [222]. Due to the capacity of producing
strong pro-inflammatory cytokines and immunomodulatory properties, C. foetida can be used to treat
COVID-19 disease.

40. Boerhavia diffusa L.
Boerhavia diffusa (B. diffusa) belongs to the family of Nyctaginaceae and is commonly known as
punarnava [282]. It is mostly found in Asian countries and is basically used for the treatment of
various diseases, such as abdominal pain, jaundice, dyspepsia, stress, spleen enlargement and liver
diseases [228]. B. diffusa bioactive components extracted from leaf, stem and root include flavonoids,
triterpenoids, alkaloids, hypoxanthine, steroids, lipids, lignin, proteins, ursolic acid, boeravinone,
punarnavoside, etc. [227,230]. However, Bose et al., 2017 suggested that B. diffusa has a strong potential
to inhibit the entry of hepatitis C virus and its major compound (boeravinone H component) were able
to block the initial phase of HCV entry through acting directly on the viral particles [228]. Moreover,
Manu et al., 2007 also showed that its second major bioactive compound (Punarnavine) was also able
to enhance the immune response, especially IFN-γ and interleukin-2 cytokines [229]. This categorizes
B. diffusa as a therapeutically important plant to be considered under the current circumstances of the
COVID-19 pandemic and worth further investigation.

41. Terminalia chebula Retz
Terminalia chebula (T. chebula) belongs to the family of Combretaceae and is mostly found in
the Asian region [283]. It is one of the most important medicinal plants due to the presence of a
huge number of different kinds of phytoconstituents [232]. It is customarily used as a household
remedy and also in modern, Ayurveda, Unani and Homoeopathic medicines [232,283]. Its bioactive
components extracted from the leaves, bark and fruit of the plant include flavonoids, polyphenols,
terpenes, anthocyanins, glycosides, gallic acid, chebulagic acid, punicalagin, chebulanin, corilagin,
neochebulinic acid, ellagic acid, chebulinic acid, alkaloids and many more [232,237,284]. It is also
known to be used as a cure for irregular fevers, urinary diseases, diabetes, skin diseases, heart diseases,
constipation, ulcers, vomiting, colic pain, hemorrhoids, digestive diseases, and others [232,235,237].
However, T. chebula has many pharmacological activities such as antiviral, antioxidant, antibacterial,
antifungal, anti-protozoal, anti-carcinogenic, anti-mutagenic, radio-protective, chemo-preventive,
hepato-protective, cardio-protective, cyto-protective, anti-diabetic, reno-protective, anti-inflammatory,
anti-arthritic, adaptogenic, anti-anaphylactic, hypolipidemic, hypocholesterolemic, anti-caries,
wound healing, anti-allergic, immunomodulatory, anti-ulcer, anti-spasmodic and gastrointestinal
motility properties [232,233,235–237]. Lin et al., 2013 conducted an in vitro study and found that
chebulagic acid and punicalagin from the fruit of T. chebula have the potential to inhibit the activity of
different viruses, such as human cytomegalovirus, HCV, dengue virus, measles virus, and respiratory
syncytial virus [234]. Due to its strong biological properties, it is highly recommended to study
T. chebula as a possible remedy against SARS-CoV-2.

42. Caesalpinia sappan L.
Caesalpinia sappan (C. sappan) belongs to the family of Caesalpiniaceae and it is usually known
as Brazil or Sappan wood [219]. It is mostly found in Southeast Asian regions and is traditionally
used for the treatment of various diseases such as tuberculosis, diarrhea, dysentery, skin infections,
anemia, etc. [219,240]. C. sappan is effectively considered as an antiviral, anti-inflammatory, antioxidant,
antibacterial, antifungal, and anti-complementary [219,240,241]. Its bioactive constituents include
xanthone, coumarin, chalcones, flavones, homoisoflavonoids, and brazilin [240]. Tewtrakul et al.,
2015, extracted nine compounds from the roots of C. sappan. The results showed that, out of those
nine, sappanchalcone (IC50 2.3 µM) and protosappanin A (IC50 12.6 µM) presented the strongest
effect against HIV-1 IN [240]. On the other hand, Liu et al., 2009 also investigated the role of this
medicinal plant against influenza virus. The in vitro study showed that 3-deoxysappanchalcone and
sappanchalcone component isolated from C. sappan exhibited the highest activity against influenza
virus (H3N2), with IC50 1.06 and 2.06 µg/mL, respectively [239]. Therefore, sappanchalcone from
C. sappan should also be considered for further examination against SARS-CoV-2.

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