Antiviral Activity of Jamaican Medicinal Plants and Isolated Bioactive Compounds

Abstract

Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders among a myriad of other ailments. The World Health Organization (WHO) estimates that over 65% of the world population solely utilize botanical preparations as medicine. Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable, convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest because it has approximately 52% of the established medicinal plants that exist on earth. This makes the island particularly welcoming for rigorous scientific research on the medicinal value of plants and the development of phytomedicine thereof. Viral infections caused by the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, and the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) present a significant global burden. This is a review of some important Jamaican medicinal plants, with particular reference to their antiviral activity.

Full text

molecules
Review
Antiviral Activity of Jamaican Medicinal Plants and Isolated
Bioactiv Compounds
Henry Lowe 1,2,3,4, Blair Steele 1, *, Joseph Bryant 1, Emadelden Fouad 5, Ngeh Toyang 2,3 and Wilfred Ngwa 5,6


Citation: Lowe, H.; Steele, B.; Bryant,
J.; Fouad, E.; Toyang, N.; Ngwa, W.
Antiviral Activity of Jamaican
Medicinal Plants and Isolated
Bioactive Compounds. Molecules
2021,26, 607. https://doi.org/
10.3390/molecules26030607
Academic Editor: Justin Jang
Hann Chu
Received: 26 October 2020
Accepted: 29 December 2020
Published: 25 January 2021
Publisher’s Note: MDPI stays neu-
tral with regard to jurisdictional clai-
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nal affiliations.
Copyright: © 2021 by the authors. Li-
censee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and con-
ditions of the Creative Commons At-
tribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
1Biotech R & D Institute, University of the West Indies, Mona, 99999 Kingston, Jamaica;
lowebiotech@gmail.com (H.L.); jbryant@ihv.umaryland.edu (J.B.)
2Vilotos Pharmaceuticals Inc., Baltimore, MD 21202, USA; ngeh.toyang@flavocure.com
3Flavocure Biotech Inc., Baltimore, MD 21202, USA
4Institute of Human Virology (IHV), University of Maryland School of Medicine, Baltimore, MD 21201, USA
5Physics Department, Florida Polytechnic Institute, Lakeland, FL 33805, USA; efouad@floridapoly.edu (E.F.);
wngwa@bwh.harvard.edu (W.N.)
6
Brigham and Women’s Hospital, Dana-Faber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
*Correspondence: blairgsteele@gmail.com; Tel.: +1-876-926-8502
Abstract:
Plants have had historical significance in medicine since the beginning of civilization.
The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants
and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers,
reproductive disorders among a myriad of other ailments. The World Health Organization (WHO)
estimates that over 65% of the world population solely utilize botanical preparations as medicine.
Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable,
convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have
been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest
because it has approximately 52% of the established medicinal plants that exist on earth. This makes
the island particularly welcoming for rigorous scientific research on the medicinal value of plants and
the development of phytomedicine thereof. Viral infections caused by the human immunodeficiency
virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, and the severe acute
respiratory syndrome coronavirus 2 (SARS CoV-2) present a significant global burden. This is a review
of some important Jamaican medicinal plants, with particular reference to their antiviral activity.
Keywords: phytomedicine; viral infections; antivirals; phytoantiviral
1. Introduction
Viral infections like the human immunodeficiency viruses types 1 and 2 (HIV-1 and
HIV-2), herpes simplex virus (HSV), respiratory viruses like; rotaviruses, respiratory syncy-
tial viruses (RSV), influenza A virus, the severe acute respiratory syndrome coronavirus
2 (SARS CoV-2) that causes the human coronavirus (COVID19), tuberculosis, and hep-
atitis B and C viruses, malaria, yellow virus fever (YVF), human papilloma virus (HPV),
dengue-virus type 2 (DENV-2) and coxsackie virus all represent a significant global bur-
den. In modern Western medicine, natural preventative and therapeutic alternatives are
increasingly gaining attention because of greater accessibility to medicinal plants, and the
possibility that they may have fewer and less adverse side-effects, are safer, and have po-
tentially greater therapeutic efficacy than synthetic drugs. These make natural alternatives
more desirable as novel drug therapies. Interest in phytoantivirals has also been renewed
because of the increasing global burden of viral infections, particularly those that are newly
emerging, and increasing antiviral resistance among viral strains against conventional
synthetic antivirals drugs like Acyclovir and Ganciclovir.
In many parts of the world, particularly in rural, developing countries, herbalism is
the only form of traditional medicine. In 2011, the WHO estimated that between 70 and 95%
Molecules 2021,26, 607. https://doi.org/10.3390/molecules26030607 https://www.mdpi.com/journal/molecules

Molecules 2021,26, 607 2 of 30
of the world population use botanical preparations as medicine [
1
]. Thousands of years of
anecdotal evidence support the medicinal claims of these plants, but for the vast majority,
rigorous scientific monitoring and research are required to study the mechanisms of action
of the bioactive compounds, and their safety and efficacy [
2
]. It is estimated that some 25%
of medicines on the global market are synthesized from natural products [
3
]. Plants from
which popularly used drugs worldwide have been derived include Ephedra sinica Stapf.
used to make methamphetamine and pseudoephedrine, Willow bark to make Aspirin,
Cannabis sativa L. to make Dronabinol
®
, Nabilone
®
and Sativex
®
,Papaver somniferum L.
(opium poppy) to make morphine, codeine and heroin, Taxus brevifolia Nutt. to make taxol,
and Vinca rosea L. to make vincristine.
Through ethnobotanical screening, thousands of plants and their biologically active
ingredients have been identified. Of the estimated 300,000 plants species that exist world-
wide, only around 15% have been evaluated for their pharmacological activity [
4
]. It is
estimated that two-thirds of the world’s plant species have medicinal value [
5
]. Between
1981 and 2019, the FDA approved more than 1500 drugs either made from unaltered
natural products, botanical drug mixtures, derivates of natural products, synthetic drugs
with pharmacophores from natural products or mimics of natural products [
6
,
7
]. In 2019,
the FDA approved 441 small molecule drugs made directly from natural products and
their derivates [7]. Refer to Table 1.
Table 1.
Drugs approved by the FDA between1 January 1981 and 30 September 2019 that were either
derived from botanical drugs, unaltered natural products, or synthetic drugs with natural pharmacophore.
Type of Drug Number Approved
Natural products 71
Botanical drugs (defined mixture) 14
Natural product mixture 356
Synthetic drugs with natural pharmacophores 207
TOTAL 648
Medicinal plants produce primary and secondary metabolites, that, in addition to
providing health benefits to humans, may have an original intended use in the plant as
biological defenses against herbivores [
8
]. The plant kingdom (including microbes, lichens,
algae, and higher plants) produces an estimated 600,000 to 700,000 phytochemicals, with at
least 150,000 to 200,000 being bioactive compounds [9].
Some active compounds in these plants responsible for the therapeutic effects of phy-
toantivirals include alkaloids, anthraquinones, coumarins, polyphenols (e.g., flavonoids),
phenolic acids and their derivatives, lignans, naphthoquinones, peptides, nitrogenated
compounds, polysaccharides and terpenes. Lipophilic terpenoids (essentials oils) disrupt
the virus envelope’s lipid double layer and may even cause it to lyse [
10
]. Polyphenols
(e.g., flavonoids) and phenolic acids may prevent the virus from docking to the host
cell [
10
]. Phytochemicals like alkaloids (e.g., quinoline), furanocoumarins, aristolochic acid,
macrozamin and cyasin can attack and mutilate nucleic acids (DNA and RNA) either by
alkylating the DNA molecule or intercalating within the DNA molecule [
10
]. Other ac-
tive ingredients that have been used in ancient/traditional medicine include strychnine,
quinine, and morphine (European medicine), camptothecin and taxol (Chinese medicine),
and Vinca alkaloids vincristine and vinblastine extracts from the Madagascar periwinkle
(Catharanthus roseus) [
11
]. Other important biologically active ingredients that have been
discovered from plants include resveratrol and curcumin.
Despite the increasing clinical research on phytoantivirals, there is need for more rigor-
ous screening of more plants to identify new phytochemicals. Further research is required
to determine the efficacy, dosage standards, optimum extraction methods/solvents, cyto-
toxicity/hepatoxicity, pharmacokinetics, molecular mechanisms of action, phytoantiviral
screening methods, and drug interactions for many phytoantivirals.

Molecules 2021,26, 607 3 of 30
Modern research around the world needs to now focus on the pharmacological activi-
ties of the constituent compounds of these plants and mapping their genomes and tran-
scriptomes to produce target drugs. These compounds include alkaloids, anthraquinones,
coumarins, polyphenols (flavonoids, tannins and rosmarinic acid), phenolic acids, lignans,
naphthoquinones, peptides, polysaccharides and terpenes.
The top five largest orders of medicinal plants include Lamiales, Rosales, Malpighiales,
Fabales and Sapindales [
12
]. The Medicinal Plant Database is a comprehensive multi-
omics database of medicinal plants [
12
]. Using sequencing technology and synthetic
biology, this genomic and transcriptomic mapping database will allow for the development
of synthetic drugs that will be able to target a certain molecular pathway in a given
disease process.
The purpose of this article is to review the state-of-the-art developments in phytomedicines
in Jamaica, with particular focus on antivirals. This should provide a valuable reference for
further studies on development and clinical translation of these phytomedicines.
2. Jamaican Plants with Medicinal Potential
Medicinally, there is increasing focus on Jamaica because of the wide diversity of
medicinal plants. Plant-based decoctions have been a significant part of Jamaican tradi-
tional folklore medicine primarily to treat the common cold, flu, headache, nausea, pain,
reproductive system disorders and digestive issues, among some of the aforementioned
diseases that are a significant global burden. Popular medicinal plants used in traditional
Jamaican folk medicine include Momordica charantia L. (Cerasee), Aloe barbadensis Miller
(Aloe vera (L.) Burm.f./), Cannabis sativa L. (Ganja), Cola acuminate (P.Beauv.) Schott and
Endl. (Bissy), Morinda citrifolia L. (Noni), Pothomorphe umbellata (L.) Miq. (Cowfoot Leaf),
Cinnamomum tamala (Buch.-Ham.) T.Nees and Eberm. (Bay leaf), Zingiber officinale Roscoe
(Ginger), Bryophyllum pinnatum (Lam.) Oken (Leaf-of-life), Moringa oleifera Lam. (Moringa),
Panax ginseng C.A.Mey. (Ginseng), Mikania micrantha Kunth (Quako), Marrubium Vul-
gare L. (White horehound/”Mint”), Andrographis paniculata (Burm.f.) Nees (Rice bitters),
Curcuma Longa L. (turmeric), Petiveria alliacea L. (Guinea Hen Weed), Camellia Sinensis (L.)
Kuntze (“Tee tree”), Alysicarpus vagilinis (L.) DC. (Medina) and Allium sativum L. (Gar-
lic). Jamaicans have used a combination of these plants for detoxing and to treat a wide
range of ailments including, but not limited to headache, nausea, pain, inflammation,
cancer, diabetes, reproductive disorders, viral infections (common cold and “flu”), arthritis
and hypertension.
The antiviral properties of these medicinal plants are supported by traditional anecdo-
tal evidence. There is a need for more scientific research to establish efficacy, pharmacologi-
cal and pharmacokinetic data and standard dosages for medical conditions. Viral infections
are the second-most identified health condition for which medicinal plants were used to
treat in Jamaica [13].
Popular in the Jamaican ethnomedical heritage is what is known as a “root tonic”
or “strong back”. This drink is a decoction of plants including, but not limited to Smi-
lax balbisiana Kunth (“chany root”), Smilax ornata (sarsaparilla), Zingiber officinale Roscoe
(“ginger”), Alysicarpus vaginalis (L.) DC. (“medina”), Morinda royoc L. (“redgal”), Desmod-
ium incanum DC. (“tick clover”), Cuphea parsonsia (L.) R.Br. ex Steud. (commonly referred
to as “strong back leaf”), Trophis racemosa (L.) Urb. (“ramoon”), and Iresine diffusa Humb.
and Bonpl. Ex Willd (“nerve west”) [
14
]. This decoction is commonly used by males to
treat impotence, and increase stamina. However, many of these plants like Z. officinale,
C. parsonsia, S. ornata, and A. vaginalis have noted antiviral activity.
Table 2shows the frequently used medicinal plants to treat the common cold and flu
in Jamaica.
A 2011 ethnomedicinal survey by Picking and colleagues investigated popular medic-
inal plants in Jamaica and confirmed the significance of plants and herbs in primary health
care in Jamaica [
13
]. This survey followed the TRAMIL network ethnomedicine method-
ology. The TRAMIL network is a Caribbean-based network of collaborators conducting

Molecules 2021,26, 607 4 of 30
scientific evaluations of medicinal plants in the region. The questionnaire was admin-
istered to 407 randomly selected adults, from randomly selected geographical clusters
across Jamaica. The survey revealed that respondents used 116 medicinal plants for vari-
ous ailments. Of these, 94% (107 plants) were distributed across fifty-one plant families.
The top five families with the most frequent plant families identified were Fabaceae,Lami-
aceae,Asteraceae,Malvaceae, and Piperacerae [
13
]. Common plants of the Fabaceae family
include Legumes, Maranga, Strong Back, Dandelion and Medina. Common herbs of the
Lamiaceae family include Basil, Sage, Rosemary, Oregano, Thyme, Mentha and Lavender.
The Lamiaceae family is commonly known as the Mint family. Some plants of the Asteraceae
family include of Marigold, Spanish Needle, and Quaco Bush. Common plants of the
Malvaceae family include Bissy, Sorrel, and Hibiscus.
Of the 107 plants identified by survey respondents, eight are endemic to Jamaica.
These are Piper amalago L. (Pepper elder), Rhytidophyllum tomentosum (L.) Mart. (“Search-
mi-heart”), Bidens reptans (L.) G.Don (“McKatty Weed”/”Marigold”), Peperomia amplexi-
caulis (Sw.) A. Dietr (“Jackie’s saddle”), Oryctanthus occidentalis (L.) Eichler (“Godbush”),
Pilea microphylla (L.) Liebm. (“Baby puzzle”), Smilax balbisiana Kunth (“Chany Root”),
and Boehmeria jamaicaensis Urb. 1907 (“Doctor Johnson”). Of these, P. amalago L. has the
most notable medicinal use [13].
The common cold, which may be caused by different viruses, has been among the
most prevalent health issues in Jamaica. Leaf of Life (B. pinnatum) and Jack-in-the bush
(Euphatorium odoratum L.) have a frequency of use of equal to or greater than 20% for these
viral infections in Jamaica [13].
A 2006 study by Mitchell and Ahmad investigated and summarized all the medicinal
plant research carried out on Jamaican medicinal plants between 1948 and 2001 at the Fac-
ulty of Pure and Applied Science, University of the West Indies (UWI), Mona, Jamaica [
15
].
Mitchell and Ahmad report that Jamaica has at least 334 medicinal plant species. However,
only 193 were tested for their bioactivity—80 plants of which were reported to have reason-
able bioactivity. Natural products were also identified from 44 of these plants. Of the plants
tested at UWI, only 31 were endemic to Jamaica. Some 23% percent of these 31 plants were
tested and found to be bioactive [15].
3. Jamaican Plants with Major Antiviral Activity
Of the many plants which have important antiviral activity, those used most frequently
in Jamaica for the common cold and influenza viruses are: Cerassee (Momordic charactia
L.), and Fevergrass (Cymbopogon citratus L.), Tamarind leaves (Tamarindus indica L.),Thyme
(Thymus vulgaris L.),Sarsaparilla (Smilax ornata Lem.), Soursop leaf (Annona muricate L.),
Pimento Leaf (Pimenta dioca (L.) Merr.), Garlic (Allium sativum L.), Leaf of Life (Bryophyllum
pinnatum (Lam.) Oken), Search-mi-heart (Rhytidophyllum tomentosum (L. Mart.), Mint
(Mentha piperita L.), Cinnamon (Cinnamomum verum J. Presl), Oregano (Oregano vulgare L.),
Papaya leaf (Carica papaya L.), and Medina (Alysicarpus vaginalis (L.) DC.). Some Jamaican
plants with major antiviral activity are shown in Figure 1and are discussed below.
3.1. Ball Moss/ “Old Man’s Beard” (Tillandsia recurvata L.)
The Tillandsia L. genus is made up of approximately 650 species and belongs to the
Bromeliaceae family endemic to North and South America and the Caribbean. Pineapples,
although of a different genus (Ananas), are also of the Bromeliaceae family. These species
differ in growth habit, trichrome distribution, type of fruit, seed, leaflet, photosynthe-
sis, type of pollinator, and its epiphytes [
16
]. T. recurvata has been used in traditional
medicine to treat kidney inflammation (Bolivia), rheumatism, ulcers and hemorrhoids
(Brazil), menstrual disorders (Mexico), eye infection (Uruguay), and Leucorrhea (USA).
Most species of the Tillandsia L. genus are epiphytes on trees, inert substrates, rocky slopes,
phone wires, electricity lines, or may survive independently in soil. It should be noted
that Tillandsia usneoides (L.) L. (“Spanish Moss”) and T. recurvata (“Ball Moss”) are not
mosses but, instead, are angiosperms—produces flowers. The primary compounds in

Molecules 2021,26, 607 5 of 30
Tillandsia genus are triterpenoids and sterols (51%), flavonoids (45%) and cinnamic acid
(4%). Lowe and colleagues discovered Dicinnamoyl-Glycerol Esters in the ball moss plant,
with both anti-cancer and anti-HIV properties (US patent #US8907117B2) [
17
]. These anti-
cancer and antiviral properties may also be due to the naturally occurring cycloartanes
found in the ball moss plant—cycloartane-3,24,25-diol and cycloartane-3,24,25-triol [
18
].
A 2020 study by Gao and colleagues also confirmed anti-HIV properties of tillandsia [
19
].
Figure 2below are examples of chemical structures of some bioactive molecules found in
Tillandsia recurvata L.
Figure 1. Some Jamaican plants with major antiviral activity.
3.2. Aloe vera (L.) Burm. f. (Aloe barbadensis Miller)
The antiviral activity of A. vera may be due to a number of phytochemicals includ-
ing vitamins, minerals, anthraquinones, polyphenols (e.g., flavonoids), polysaccharides,
phenolic acids and sterols [
20
]. A 2018 study by Gansukh and colleagues investigated the
anti-influenza activity of flavonoids and phenolics found in A. vera [
21
]. A 5 min ultrasonic
water extraction of aloe emodin, an anthraquinone prepared from aloin from the A. vera
plant, showed anti-influenza activity with zero cytotoxicity [
21
]. Aloe emodin was also
able to inactivate herpes simplex virus types 1 and 2, varicella-zoster virus, pseudorabies
virus, and the influenza virus, by partial destruction of the virus’ envelope [
22
]. Lectins,
extracted from the gel portion of the leaves of A. vera, also showed antiviral activity against
the human cytomegalovirus (CMV) in cell culture [23].

Molecules 2021,26, 607 6 of 30
Figure 2. Chemical structures of some bioactive molecules found in Tillandsia recurvata L.
A. vera anti-HSV-1 activity was also assessed and confirmed in a 2016 study by Reza-
zadeh and colleagues [
24
]. A preparation of A. vera gel showed significant (0.2-5%) inhi-
bition of herpes simplex virus-1 cells isolated from the lip lesions of a patient and grown
cell culture (Vero cells) [
24
]. A. vera was also shown to inhibit HSV-2 attachment and
post-attachment processes, and entry into Vero cells [
25
]. Figure 3below are examples of
chemical structures of some bioactive molecules found in A. vera.
Figure 3. Chemical structures of some bioactive molecules found in A. vera.
3.3. Ganja (Cannabis sativa L.)
It is estimated that C. sativa produces an estimated 545 [
26
] chemical compounds be-
longing to biogenetic classes [
27
]. Of these compounds, the two most prominent and most
studied are the secondary metabolites (phytocannabinoids)—
∆9
-tetrahydrocannabinol
(
∆9
-THC) and cannabidiol (CBD), both of which have a wide therapeutic window against
many ailments. In addition to these secondary metabolites, C. sativa produces hundreds of
non-cannabinoids secondary metabolites, also with a wide range of therapeutic applicabil-
ity against many ailments. These include terpenoids, flavonoids, stilbenes, lignans, and al-
kaloids [
28
]. Some of these phytochemicals have antiviral activity. Dihydro-resveratrol,
a metabolite of trans-resveratrol, an antiviral found in grapes, is also found in cannabis [
27
].
Terpenes like limonene and ocimene have also been reported to demonstrate antiviral activ-

Molecules 2021,26, 607 7 of 30
ity [
29
,
30
]. A 2020 study by Ngwa and colleagues reported that a small antiviral flavonoid
molecule Caflanone has selective activity against the human coronavirus hCov-OC43
(COVID-19) disease [31].
Cannabidiol (CBD) is one of 100 pharmacologically active terpenophenic/lipophilic com-
pounds called Cannabinoids—found in C. sativa. CBD It is the major non-psychoactive/non-
intoxicating component of the cannabis plant. This simply means that it does not get you
“high”. CBD still, however, retains its therapeutic properties and benefits.
CBD can be used to regulate the immune system’s response to viruses (and other
invading pathogens. The immune system uses oxidative stress (via reactive oxygen species)
to combat invading pathogens. During many disease processes, the cells of the body accu-
mulate high levels of reactive oxygen species (R.O.S.). This may be due to reasons including,
but not limited to increased metabolic activity, increased oxidase activity, and/or increased
mitochondrial activity. In excess, oxidative stress can cause tissue and organ damage.
Numerous studies show CBD’s potential as an anti-oxidant. CBD inhibits neurotoxicity
and oxidative stress by reducing inflammation, production of reactive oxygen species and
other oxidative stress parameters [
32
] associated with infections by pathogens. A proposed
mechanism of action of CBD is the amelioration of ROS production. When oxygen is metab-
olized in the body, ROS is produced. In moderation, ROS is involved in homeostasis and
signaling and is associated with the maintenance of healthy cells [
32
]. Antioxidants like
CBD mitigate excessively produced reactive oxygen species within the cells, and in doing
so, reduce the oxidative stress in cells [
5
]. Antioxidants may therefore have therapeutic
applicability against many human diseases including but not limited to viral infections,
but also cancer cardiovascular diseases and inflammatory diseases [
5
]. Figure 4below are
examples of chemical structures of some bioactive molecules found in C. sativa L.
Figure 4. Chemical structures of some bioactive molecules found in C. sativa L.

Molecules 2021,26, 607 8 of 30
3.3.1. Cannabidiol (CBD) and HIV/AIDS
CBD is used to alleviate the wasting syndrome associated with HIV and AIDS [
33
].
It is used as an antiemetic and orexigenic agent (appetite stimulant), and may generally
just improve the overall quality of life of an HIV/AIDS patient. Anecdotal evidence
suggests that CBD in HIV/AIDS patients may improve appetite, reduce nausea and
vomiting, increase caloric intake, promote weight gain, improve memory and dexterity,
improve mood, and mitigate the negative side effects of current anti-retroviral therapeutic
agents [
33
]. In terms of disease progression (morbidity) and delaying the likelihood of
death from HIV/AIDS, current studies show that CBD is not effective [33].
3.3.2. Cannabidiol (CBD) and Hepatitis Viruses
Liver disease in general, is a major global health burden. Viral hepatitis is a disease
of the liver characterized by liver inflammation and damage as a result of viral infection.
Viral hepatitis is commonly caused by one of five hepatotropic viruses (hepatitis A, B, C,
D and E), but may be caused by other viruses like the herpes simplex virus (HSV) Yellow
fever virus (YFV), cytomegalovirus (CMV) and Epstein–Barr virus (EBV). Hep A, Hep B,
and Hep C are the most common causes of viral hepatitis. Hep A and Hep E are spread by
the fecal-oral route, that is, contamination via contaminated food or water. Hep B, Hep C
and Hep D are spread through blood transfusion. There is evidence that these may also be
spread sexually.
Hepatitis may also be caused by other types of micro-organisms including bacteria,
fungi and even parasites, non-infectious agents like drugs and alcohol, and other metabolic
and autoimmune diseases [
34
]. Hepatitis infections may either be acute (short-term),
where the body will be able to resolve the infection or chronic (long-term), where the body
is unable to resolve the infection, resulting in liver failure, liver cirrhosis and liver cancer.
In a 2017
in vitro
study by Lowe and colleagues explored the bioactivity of CBD
against hepatitis B and C viruses [
35
]. The anti-hepatitis B assay was carried out using
HepG2 2.2.15 cells that produce high levels of the HBV wild-type ayw1 strain. The anti-
hepatitis C assay utilized Huh7.5 cells mixed with cell-culture derived HVC. In both assays,
cells were plated in a 96-well microtiter plate. A single concentration of 10
µ
M of the
test compound (CBD) was then added to both microtiter well plates, incubated, and an
analysis of antiviral activity was determined by calculating the percent of inhibition of viral
replication. CBD was shown to have inhibitory effects against viral hepatitis C (HBC) but
not viral Hepatitis B (HBV). In a dose–response assay, at a single concentration of 10
µ
m,
CBD was able to dose-dependently inhibit HCV replication by 86.4% [
35
]. CBD also seems
to have therapeutic efficacy against autoimmune/non-viral hepatitis [
35
]. CBD shows
in vivo
activity through its interaction with the CB2 receptor. This interaction inhibits
the pathogenesis of autoimmune hepatitis by inducing the apoptosis of thymocytes and
splenocytes. This in turn, inhibits T-cells and macrophages attacking the liver thereby
inhibiting the release of pro-inflammatory cytokines [35].
Myeloid-derived suppressor cells (MDSCs) are responsible for regulating the immune
system by suppressing T-cell function and inhibiting liver inflammation. Through interac-
tion TRPV1 receptor, CBD is shown to activate MDSCs, thereby inhibiting inflammation
and hepatitis in a murine model [
36
]. In a concanavalin A model of acute hepatitis in mice,
Hegde and colleagues report that CBD was able to reduce ConA-induced inflammation by
inhibiting the production and release of various pro-inflammatory cytokines, and protect
the mice from acute liver injury [36].
3.3.3. Caflanone (a Non-Cannabinoid Secondary Metabolite Found in C. sativa L.)
Caflanone is a small phytoantiviral flavonoid molecule with selective activity against
the human coronavirus hCov-OC43 (COVID-19) disease belonging to clade b of the genus
Betacoronavirus same as SARS-COV-2 [
34
]. In preclinical studies, Caflanone inhibited the
hCov-OC43 human Coronavirus with an EC50 of 0.42
µ
M [
31
]. In silico studies show that
the Caflanone molecule carries out its prophylactic mechanism of action by inhibiting the

Molecules 2021,26, 607 9 of 30
Angiotensin-converting enzyme 2 (ACE2) receptor found in the lung and respiratory tract,
used by the virus to cause an infection [
31
]. Caflanone was also shown to have strong
binding affinity to two of the proteases (PLpro and 3CLpro) are vital to the replication
of SARS-COV-2 in humans, which would inhibit viral entry to and/or replication within
human cells [31].
The following phytoantivirals were investigated and compared to Chloroquine (CLQ),
a potential COVID-19 prophylactic and therapeutic agent currently in clinical trials. The
docking/binding studies results below show that the phytoantiviral flavonoids (Hesperetin,
Myricetin, Linebacker, and Caflanone) could bind equally or more effectively than CLQ [
31
].
3.3.4. Terpenoids of Cannabis Sativa L. as Antiviral Agents
The Medical Cannabis Network of Israel also reports that a current study is being under-
taken by researchers at the Israel Institute of Technology investigating the therapeutic efficacy
of a cannabis terpene inhalant formulation in suppressing the immune system response
against COVID-19 [
37
]. A molecular docking analysis also reported the antiviral activity of
Ginkgolide A, a terpenoid produced by the Ginkgo biloba tree, against COVID-19 [38].
4. Guinea Hen Weed (Petiveria alliacea L.)
P. alliacea is a herbaceous shrub belonging to Petiveriaceae, the pigeonberry family.
It is native to tropical regions like Africa, India, the Caribbean, tropical areas of North
and Central America. P. alliacea produces a number of bioactive compounds including
polyphenols, alkaloids, tannins, coumarins, steroids, essential oils, dibenzyl trisulfide,
and flavonoids [
39
]. These phytochemicals are responsible for Guinea Hen Weed’s wide
therapeutic window as an anxiolytic, anticonvulsant, antinociceptive, neuroprotector,
cognitive enhancer, and antidepressant [39].
Dibenzyl trisulfide/DTS (C
14
H
14
S
3
) in the Guinea Hen Weed is responsible for its
anti-cancer, ant-HIV, and anti-hepatitis C properties [
40
,
41
]. Figure 5below should the
chemical structure of dibenzyl trisulfide (DTS) found in Guinea Hen Weed.
Figure 5. Chemical structures of dibenzyl trisulfide (DTS) found in Guinea Hen Weed.

Molecules 2021,26, 607 10 of 30
The anti-cancer and antiviral properties of this compound may be due to its inter-
action with the mitogen-activated protein, extracellular-regulated kinases 1 and 2 (MAP
Kinases Erk 1/Erk2) pathway [
41
] (Figure 6). The mechanism by which DTS inhibits HIV-1
activity is by inhibition of the reverse transcriptase (RT) activity of the HIV-1 virus [
40
]
(Figure 7). Anecdotal evidence also suggests that Guinea Hen Weed may also be used to
combat the influenza viruses. DTS has also been reported to demonstrate anti-hepatitis
C virus properties responsible for hepatocellular carcinoma [
42
]. However, the molecular
mechanism of action has not yet been elucidated.
Figure 6.
A possible antiviral mechanism of DTS in an infected cell. The mitogen-activated protein
kinase/extracellular signal-regulated kinase (MAPK ERK1/ERK2 pathway) is a signaling pathway
that is responsible for the transduction of protein components (chemical signals, transcription
factors), MAP kinase kinase (MAP2K), and a final kinase, MAP kinase (MAPK), leading to the
functioning and regulation of multiple cellular processes like cell proliferation, cell growth, and cell
survival. A dysregulation of this pathway or any of its components typically has pathological
consequences [
43
,
44
]. It has been proposed that some pathological conditions are characterized by
increased phosphorylation of kinases [
45
], possibly resulting in over-proliferation of cells. Dibenzyl
trisulfide (DTS) is shown to inhibit the MAPK ERK1/ERK2 pathway in cancer- and (possibly)
virally infected cells via dephosphorylation of ERK1/2, ultimately resulting in apoptosis of the
cell [
45
]. MAP—mitogen-activated protein; K—kinase; Raf—rapidly accelerated fibrosarcoma; MEK—
mitogen-activated protein kinase.

Molecules 2021,26, 607 11 of 30
Figure 7. A possible anti-HIV-1 mechanism of DTS in a CD4 cell.
5. Ginger (Zingiber Officinale Roscoe)
Ginger is frequently used in Jamaica as an antiemetic and antinauseant. In addition
to having antioxidant, antimicrobial, anti-inflammatory, and anticoagulant properties,
fresh ginger, as opposed to dried, has also been reported to be antiviral, inhibiting human
respiratory syncytial virus-induced plaques in human upper (HEp-2) and low (A549)
respiratory tract cell lines [46].
The bioactive compounds in ginger that are responsible for the wide therapeutic win-
dow of ginger include gingerols (like shogaols, 6-, 8- and 10- gingerol), paradols, ketones,
phenolic compounds (like 6-dehydrogingerdione, zingerone, quercetin, and gingerenone-
A), terpenes (like
α
-curcumene,
α
-farnesene,
β
-bisabolene and
β
-sesquiphellandrene),
esters, aldehydes, and alcohols [
47
]. Figure 8a–e are examples of bioactive molecules found
in Zingiber officinale Roscoe and their chemical structures.
A possible mechanism of antiviral action of ginger is the blocking of viral attachment
and internalization via stimulation of mucosal cells of the respiratory tract to secrete
interferon-
β
(IFN-
β
) [
46
] (Figure 9). Ginger has also been reported to demonstrate
antiviral properties against the hepatitis C virus (HCV) [47].

Molecules 2021,26, 607 12 of 30
Figure 8. Chemical structures of some bioactive molecules found in Zingiber officinale Roscoe.
Figure 9.
A possible antiviral mechanism of ginger (Zingiber officinale Roscoe). It is possible that
ginger blocks viral attachment and internalization via stimulation of mucosal cells of the respiratory
tract to secrete interferon-β(IFN-β) [46].
6. Turmeric (Curcuma Longa L.)
Turmeric (Curcuma longa L.) is the belowground portion (rhizome) of the ginger
plant, of the family Zingiberaceae. Turmeric is a widely used spice, food preservative,
food coloring and dye but has also been employed for its medicinal value [
48
]. It has a
wide therapeutic window as an antiviral, aseptic, antibacterial, antifungal, anti-cancer, anti-
phlegmatic antiprotozoal, antioxidant, anti-inflammatory, antifibrotic, antifertility, antiulcer,
antivenom, anticarcinogenic and anticoagulant [
48
]. In traditional Eastern medicine it is

Molecules 2021,26, 607 13 of 30
used to treat respiratory ailments, eating disorders, digestive disorders, hepatic disorders
and biliary disorders [48].
The primary phenolic compounds (curcuminoids) produced by turmeric are curcumin
(diferuloylmethane), demothoxycurcumin and bisdemethoxycurcumin [
48
]. Other bioac-
tive compounds produced include sodium curcuminate, essential oils (e.g., turmerone,
zingiberene and sesquiterpines), monoterpenoids, and sesquiterpenoids. In addition to be-
ing an antiviral, curcumin is anti-inflammatory, anti-tumorigenic and anti-oxidant [
49
]. It is
also responsible for the orange–yellow color of turmeric. Figure 10 displays the chemical
structure of curcumin.
Figure 10. Chemical structure of curcumin (diferuloylmethane) found in Curcuma Longa L.
An
in vitro
study reported the antiviral activity of curcumin against three major
molecular pathways responsible for Epstein–Barr virus (EBV) reactivation, and was shown
to inhibit the transcription of BamH fragment Z left frame 1 (BZLF1) gene [
50
] which
plays a significant role in lytic EBV DNA replication. The anti-HIV-1 activity of curcumin
was also assessed and confirmed via inhibition of the HIV-1 integrase [
51
] (Figure 11).
Turmeric was also shown to display slight antiviral activity against respiratory viruses.
Figure 11.
A possible anti-HIV-1 mechanism of curcumin by inhibition of HIV-1 integrase. This pre-
vents integration of HIV-1 DNA into host cell DNA and ultimately inhibition of viral replication,
assembly, budding and infection of new cells.

Molecules 2021,26, 607 14 of 30
A 2007 study by Huang and colleagues demonstrated activity against the influenza
viruses, parainfluenza viruses 1, 2 and 3, adenovirus, and respiratory syncytial virus [
52
].
Curcumin was also reported to inhibit H1N1, H6N6, herpes virus, coxsackievirus B3
(CVB3), human T-cell leukemia virus type 1, hepatitis C virus, high risk human papillo-
maviruses 16 and 18 (HPV-16 and HPV-18) [53].
7. Moringa (Moringa oleifera Lam.)
M. oleifera is popular tree native to India where it is widely eaten as a vegetable and
utilized in traditional medicine. It is also used in the Western hemisphere for the same
purposes. Moringa has a wide window of benefits, due primarily to bioactive compounds
like phenolic compounds, saponins, tannins, amino acids, proteins, phytates, tocopherols
(
γ
and
α
), carbohydrates, unsaturated fatty acids, oils, antioxidant compounds, and glu-
cosinolates [
54
]. Other bioactive compounds include vitamins A, B1, B2, B3, B7, C, D, E,
K, calcium, potassium, iron, magnesium, phosphorus and zinc [55]. The pharmacological
compounds found in the moringa plant have medicinal properties including antimicrobial
activity against viruses, bacterial, fungi and parasites. It is also generally known to boost
the immune system.
Leaf extracts from Moringa oleifera showed anti-herpetic activity and were reported
to successfully inhibit the growth of HSV-1 and 2 in Vero cells by 43.2 and 21.4%, respec-
tively [
56
]. Ethanolic leaf extracts of Moringa oleifera were also reported to have anti-
influenza activity
in vitro
[
57
]. A 1998 study by Murakami and colleagues reported that
niaziminin, a thiocarbamate, 4-[(4
0
-O-acetyl-alpha-L-rhamnosyloxy)benzyl] isothyanate
(ITC) and allyl- and benzyl-ITC (two isothyanate-related compounds), were all able to
inhibit Epstein–Barr virus (EBV)
in vitro
[
58
]. Figure 12 shows the chemical structures of
niaziminin, allyl-ICT, and benzyl-ICT.
Figure 12. Chemical structures of some bioactive molecules found in Moringa oleifera Lam.
In another
in vitro
study, the effects of an aqueous extract of M. oleifera (leaves) were
able to decrease the expression of hepatitis B virus genotypes C and H in Huh7 cells [59].
8. Lignum Vitae (Guaiacum officinale L.)
The Lignum vitae (which translates to “wood of life”) is native to the Caribbean and
South America. The wood has many industrial purposes, for example to make furniture.
The flower is the national flower of Jamaica. In tradition Caribbean medicine, it is used
as a stimulant, antiseptic, and to treat syphilis [
60
]. In Trinidad and Tobago, it is used
to control fertility [
60
]. A 2014 study by Lowe and colleagues screened and investigated

Molecules 2021,26, 607 15 of 30
the anti-HIV properties of leaf, seed and twig extracts of the lignum vitae plant biomass
against HIV-1 (strain HIV-1 BaL) infected peripheral blood mononuclear cells (PBMCs) [
61
].
The main pharmacological compounds in this plant are saponins, including guaianin A,
guaianin B and guaianin N [
61
]. All the types of extracts/compounds tested inhibited
HIV-1 replication in the infected PBM cells. Figure 13 shows chemical structures of some
bioactive molecules found in lignum vitae.
Figure 13. Chemical structures of some bioactive molecules found in Lignum Vitae.
9. Garlic (Allium sativum L.)
A. sativum is a member of the onion genus, Allium. It is another spice that is traditionally
used in fundamental dishes around the world, but has also been used in traditional medicine
for thousands of years. It has a wide therapeutic window as an antiviral, antioxidant and
antibacterial against both Gram-negative and Gram-positive bacteria, antifungal activity
against Candida albicans, and is antiprotozoal against Giardia lamblia and Entamoeba histolyt-
ica [
62
]. Anecdotal and scientific data also confirm garlic’s therapeutic efficacy against
diabetes, cancer, free-radical damage, atherosclerosis, heavy metal intoxication and hyper-
lipidemia. Garlic produces many bioactive compounds including flavonoids, enzymes,
fructo-oligosaccharides, Maillard reaction products, and organosulfur compounds like
S-allylcysteine, diallyl polysulfides, alliin, vinyldithins, allicin (diallyl thio-sulfinate), al-
lyl methyl thiosulfinate, and ajoene [
63
]. These are responsible for garlic’s wide therapeutic
window, including as an antiviral against influenza A and B, HSV-1 and HSV-2, common cold,
and viral pneumonia among other respiratory viruses [
64
]. Figure 14 is a graphical repre-
sentation of the conversion of organosulfur compounds in garlic. Organosulfur compounds
demonstrate antiviral activity via inhibition of various stages of the general virus life cycle includ-
ing viral attachment, entry and multiplication [
64
] (Figure 15). Figure 16a–d show the chemical
structures of some bioactive molecules found in garlic.

Molecules 2021,26, 607 16 of 30
Figure 14. The conversion of organosulfur compounds in garlic [64].
Figure 15.
Possible anti-influenza mechanisms of garlic. Organosulfur compounds produced by
garlic may inhibit various stages of the general virus life cycle including viral attachment, entry and
multiplication [
65
]. Another possible mechanism of action is via inhibition of components of viral
signaling pathways [65].
These compounds are released and may be extracted from the cells of fresh, crushed gar-
lic bulbs, and are responsible for the characteristic garlic smell. This is why it is usually
eaten raw. Allicin is the main bioactive compound found in garlic [
62
]. The bioactivity of
allicin and other organosulfur compounds may be attributed to their chemical interaction
with thiol groups of other molecules [65].

Molecules 2021,26, 607 17 of 30
Figure 16. Chemical structures of some bioactive molecules found in garlic.
A 2009 study by Mehrbod and colleagues reported garlic’s antiviral activity against
the influenza virus
in vitro
[
65
], further confirming the anecdotal evidence for its frequency
of use in Jamaica against the flu and to “boost the immune system”. Garlic is frequently
used in Jamaica to treat the common cold, too. A 2001 study by Josling evaluated an
allicin-containing supplement against the common cold and confirmed this bioactivity [
66
].
In another study, an aged garlic extract supplement was reported to boost the immune
system by inducing NK cell function and proliferation of
γδ
-T cells [
67
].
In vitro
studies
of garlic extracts were also shown to produce anti-influenza B and anti-herpetic activity
(anti-HSV-1) [68]. This bioactivity was dose-dependent.
Further studies are required to assess the antiviral activity of garlic in human and
animals. Garlic is also reported to be good for the cardiovascular system, having the
ability to lower systolic blood pressure and ultimately treat uncontrolled hypertension [
69
].
A 2013 study by Ashraf and colleagues also confirm garlic’s dose-dependent and duration-
dependent ability to significantly lower both systolic blood pressure and diastolic blood
pressure [
70
]. Garlic is further reported to be good for lowering cholesterol and thus may
be used to treat hypercholesterolemia (a form of hyperlipidemia) [71].
10. Sorrel (Hibiscus sabdariffa L.)
In Jamaica the fresh calyx of the flower of sorrel is commonly made into a drink and
eaten in salads. However, it possesses significant medicinal value and may have appli-
cability as a diuretic, sedative, emollient, demulcent antiscorbutic, analgesic, purgative,
antipyretic, cholagogue, antiseptic, anti-tumorigenic, anti-cancer, aphrodisiac, and may
be used to treat dyspepsia, disorders of the heart, hypertension, biliary disorders and
abscesses [
72
]. Sorrel is also known for antimicrobial, antioxidant, and anti-inflammatory
properties. The antiviral activity of sorrel was also assessed and shown to inhibit HSV-2
in vitro
with safe cytotoxicity [
73
]. Sorrel was also reported to have anti-human influenza
A virus activity
in vitro
[
74
]. This bioactivity attributed to sorrel may be attributed to a
number of secondary metabolites including saponins, flavonoids (e.g., quercetin, gossyp-
itrin and hibiscetin-3-glucoside, organic acids (e.g., protocatechuic, malic acid, hydrox-
ycitric acid, and hibiscus acid), anthocyanins (e.g., anthocyanidin and delphinidin-3-O-

Molecules 2021,26, 607 18 of 30
sambubioside), glycosides, alkaloids, phenolic acids and phenolic compounds
(e.g.,
α
-tocopherol) [
75
,
76
]. Some of these secondary metabolites and their chemical struc-
tures are shown in Figure 17 below.
Figure 17. Chemical structures of some bioactive molecules found in sorrel.

Molecules 2021,26, 607 19 of 30
Table 2. Summary of frequently used medicinal plants in Jamaica.
Plant Origin Anti-Viral Window Part of Plant Used to
Make Preparation Method of Preparation/Admin Proposed Antiviral
Mechanism (s)
1.
Ginger (Zingiber officinale
Roscoe)
Native to Asia.
Cultivated widely
in Jamaica.
Anti-viral activity against the
respiratory syncytial virus
(RSV) [46], hepatitis C virus
(HCV) [47], common cold
(anecdotal), and the human
influenza viruses (anecdotal).
Root Nodule/Rhizome
Decoction made from 1 tsp or
~1 inch of fresh root nodule
brewed in 1 cup of water. Steep
for ~10 min. Sweeten as desired.
This is to treat the common cold
and flu.
Inhibition of viral attachment
and internalization via
stimulation of mucosal cells of
the respiratory tract to secrete
interferon-β(IFN-β) [46].
2. Turmeric (Curcuma longa
L.)
Cultivated (Not
indigenous to Jamaica)
Anti-viral activity
againsthepatitis C virus
(HCV), Epstein–Barr virus
(EBV) [50], HIV-1 [51], human
influenza viruses- H1N1,
H6N6 [53], parainfluenza
viruses 1, 2 and 3 [53],
vesicular stomatitis virus
(VSV) [53] and respiratory
syncytial virus [53].
Root Nodule/Rhizome
Decoction made from 1 tsp or
~1 inch of fresh root nodule
brewed in 1 cup of water. Steep
for ~10 min. Sweeten as desired.
This is to treat the common cold
and flu.
Inhibition of Epstein–Barr virus
BZLF1 transcription in Raji
DR-LUC cells [50].
Inhibition of HIV-1
integrase [51].
3.
Ball Moss/ “Old Man’s
Beard”
(Tillandsia ecurvata L.)
Indigenous to Jamaica
Anti-viral activity against
HIV [17–19], common cold
(anecdotal),and flu (anecdotal)
Leaf (Fresh or dried)
Decoction made from 1 tsp or
~1 inch of fresh root nodule
brewed in 1 cup of water. Steep
for ~10 min. Sweeten as desired.
This is to treat the common cold
and flu.
Mechanism of antiviral
activity unknown.
4. A. vera (Aloe barbadensis
Miller)
Cultivated (Not
indigenous to Jamaica)
Anti-viral activity against the
human influenza viruses
[21,22], varicella-zoster virus
(VZV) [22], cytomegalovirus
(CMV) [22], pseudorabies
virus [22], herpes simplex
virus types 1 and 2 (HSV-1
and -2) [24,25], and common
cold (anecdotal)
Inner-leaf, gel-like pulp.
Juice made of inner gel-like
pulp. This is to treat the
common cold and flu.
Partial destruction of the virus’
envelope (herpes simplex virus
types 1 and 2, varicella-zoster
virus, pseudorabies virus, and
the influenza virus) [22].
Inhibition of HSV-2 attachment
and post-attachment processes,
and entry into Vero cells [25].

Molecules 2021,26, 607 20 of 30
Table 2. Cont.
Plant Origin Anti-Viral Window Part of Plant Used to
Make Preparation Method of Preparation/Admin Proposed Antiviral
Mechanism (s)
5. Ganja
(Cannabis sativa L.)
Cultivated
(Not indigenous
to Jamaica.
Indigenous to
Central Asia)
Anti-viral activity against
HIV/AIDS wasting syndrome
[33], hepatitis viruses [35],
human coronavirus [34], and
common cold (anecdotal).
Leaf (Fresh or dried)
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired. This is to
treat the common cold and flu.
Cannabidiol (CBD) inhibits
replication of hepatitis B and C
viruses [35]. CBD also inhibits
the pathogenesis of
autoimmune hepatitis by
inducing the apoptosis of
thymocytes and splenocytes [
35
].
Caflanone inhibits the human
coronavirus (hCov-OC43) via
inhibition of the
Angiotensin-converting enzyme
2 (ACE2) receptor found in the
lung and
respiratory tract [31].
6. Guinea Hen Weed
(Petiveria alliacea L.)
Cultivated (Not
indigenous to Jamaica.
Native to Central and
South America)
Anti-viral activity against HIV
[
40
], common cold (anecdotal),
human influenza viruses
(anecdotal), and hepatitis C
virus (HCV) [42].
Whole plant (roots stem,
and leaves (fresh
or dried)
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired. This is for
the common cold and flu.
DTS inhibits HIV-1 activity is by
inhibition of the reverse
transcript-tase (RT) activity of
the HIV-1 virus [40].
7.
Moringa (Moringa oleifera
Lam.)
Cultivated (Not
indigenous to Jamaica.
Native to South Asia)
Anti-viral activity against the
human influenza viruses
(anecdotal), HSV-1 and 2 [56],
Epstein–Barr Virus (EBV) [58],
and hepatitis B virus
(HBV) [59].
Leaf (primarily dried)
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired. This is for
the common cold and flu.
The antiviral mechanism of
action is unknown.
8. Lignum Vitae
(Guaiacum officinale L.)
Cultivated (Native to the
Caribbean)
Anti-viral activity against
HIV [61], common cold
(anecdotal), and
flu (anecdotal).
Flowers, Leaves (fresh or
dried), Powdered bark,
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired. This is for
the common cold and flu.
The antiviral mechanism of
action is unknown.
9.
Garlic (Allium sativum L.)
Cultivated (Native
to Asia)
Anti-viral activity against the
human influenza viruses
(anecdotal), parainfluenza
virus type 3, HSV-1 and -2 [
64
],
and common cold (anecdotal).
- Raw bulb (most
effective), Cooked,
Supplement, or
garlic extract.
Eat or cook raw bulb (2–3) to
combat the common cold and
flu viruses.
The antiviral mechanism of
action is unknown.

Molecules 2021,26, 607 21 of 30
Table 2. Cont.
Plant Origin Anti-Viral Window Part of Plant Used to
Make Preparation Method of Preparation/Admin Proposed Antiviral
Mechanism (s)
10. Sorrel (Hibiscus sabdariffa
L.)
Cultivated (Not native
to Jamaica)
Anti-viral activity against
HSV-2 virus [73], and human
influenza viruses [74],
Common cold
(anecdotal),
Calyx
Juice made from calyx. Calyx is
left to brew overnight in boiled
water, cooled and strained, then
sweetened to taste.
The antiviral mechanism of
action is unknown.
11.
“Search-mi-heart”
(Rhytidophyllum
tomentosum (L.) Mart.
Cultivated. Native to
South America and
the Caribbean
Common cold and flu
(anecdotal) Leaf (primarily dried)
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired.
The antiviral mechanism of
action is unknown.
12. Pepper elder (Piper
amalago L.)
Cultivated (Not native to
Jamaica)
Common cold and flu
(anecdotal) Fresh Leaves
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired.
The antiviral mechanism of
action is unknown.
13.
McKatty
Weed/Marigold (Bidens
reptans L.) G.Don
Cultivated (Not native to
Jamaica)
Common cold and flu
(anecdotal)
Flowers and/or Leaves
(primarily dried)
Decoction made of 1 tbsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired.
The antiviral mechanism of
action is unknown.
14.
Chany Root a.k.a.
Jamaican Sasparilla
(Smilax balbisiana Kunth)
Native to
Jamaica
Common cold and flu
(anecdotal) Root
Decoction or tonic made of
pre-soaked roots brewed in
1 cup of water. Steep for
~10 min. Sweeten as desired.
The antiviral mechanism of
action is unknown.
15. Lemongrass/Fevergrass
(Cymbopogen citratus L.)
Cultivated (Not native to
Jamaica)
Common cold and flu
(anecdotal) Leaf (Fresh or dried)
Decoction made from a handful
of fever grass leaves and stems
in 1 cup of water. Steep for
~10 min. Sweeten as desired.
The antiviral mechanism of
action is unknown.
16. Cerasee
(Momordica charantia L.)
Cultivated (Not native to
Jamaica. Native to Africa
and Middle East)
Common cold and flu
(anecdotal)
Leaf (Fresh or dried)
and stems
Decoction made from a handful
of cerasee leaves and stems in
1 cup of water. Steep for
~10 min. Sweeten as desired.
The antiviral mechanism of
action is unknown.
17. Soursop
(Annona muricata L.)
Cultivated (Not native to
Jamaica. Native to South
America)
Common cold and flu
(anecdotal) Leaf (Fresh or dried)
Decoction made from 2–3 leaves
in 1 cup of water. Steep for
~10 min. Sweeten as desired.
The antiviral mechanism of
action is unknown.

Molecules 2021,26, 607 22 of 30
Table 2. Cont.
Plant Origin Anti-Viral Window Part of Plant Used to
Make Preparation Method of Preparation/Admin Proposed Antiviral
Mechanism (s)
18. Leaf of life (Bryophyllum
pinnatum (Lam.) Oken
Cultivated (Not native to
Jamaica. Native to
Africa)
Common cold and flu
(anecdotal) Leaf (Fresh or dried)
Decoction made from 2–3 leaves
in 1 cup of water. Steep for
~10 min. Sweeten as desired.
The antiviral mechanism of
action is unknown.
19.
Dogblood (Rivina humilis
L.)
Cultivated (Not native to
Jamaica)
Common cold and flu
(anecdotal)
Whole plant, but
primarily leaf (Fresh or
dried) and stem
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired.
The antiviral mechanism of
action is unknown.
20.
Lime Leaf Tea
(Citrus aurantiifolia
(Christm.)
Swingle
Cultivated (Not native to
Jamaica. Native to Asia)
Common cold and flu
(anecdotal) Leaf (Fresh or dried)
Decoction made 5–6 leaves in
1 cup of water. Steep for
~10 min. Sweeten as desired.
The antiviral mechanism of
action is unknown.
21. Jack-in-the-bush
(Eupatorium odoratum L.)
Cultivated (Not native to
Jamaica.
Common cold
(anecdotal)
Leaf (Fresh or dried) and
stem
Decoction made of 1–2 tsp of
dried leaves brewed in 1 cup of
water. Steep for ~10 min.
Sweeten as desired.
The antiviral mechanism of
action is unknown.
The effective dosage of each medicinal plant preparation is currently unknown. There is not enough rigid scientific research to recommend a standard dosage for any medical condition. Anecdotal evidence
recommends one to two cups of oral administration of these decoctions per day, until symptom relief is experienced.

Molecules 2021,26, 607 23 of 30
11. Toxic Compounds and Adverse Side-Effects
A limitation to homemade decoctions and infusions is due to the fact that, water,
regarded as a universal solvent, will, in addition to dissolving plant material, also dissolve
unwanted material such as contaminants and toxic compounds. These may have adverse
side-effects if ingested. On this tangent, it is of importance that herbs used to make
decoctions are grown in a suitable environment. Table 3below lists some toxic compounds
and adverse side-effects associated with frequently used medicinal plants in Jamaica.
Table 3. Some toxic compounds and adverse side-effects associated with frequently used medicinal plants in Jamaica.
Plant Possible
Contaminants
Type of Medicinal
Preparation Side-Effects
1. Ginger
(Zingiber officinale Roscoe)
Mycotoxins,
Aflatoxins
Ochratoxin A (OTA).
Microbes.
Chemical residues (pesticides)
Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach,
heartburn, diarrhea, dizziness
2. Turmeric
(Curcuma longa L.)
Lead,
Chromium,
Lead chromate (often used as a
yellow coloring).
Microbes.
Chemical residues (pesticides)
Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach,
heartburn, diarrhea, dizziness
3.
Ball Moss/ “Old
Man’s Beard”
(Tillandsia recurvata L.)
Various contaminants because of
the plant’s
bioremediatory properties.
Dependent on
growth environment.
Microbes.
Chemical residues (pesticides).
Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach,
diarrhea, and dizziness.
4. A. vera
(Aloe barbadensis Miller)
Various heavy metals like copper,
lead, Chromium, mercury, nickel,
arsenic, and cadmium.
Microbes.
Chemical residues (pesticides).
A. vera is a phytoremediator/
biosorbent [77].
Decoction or Juice
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, laxative effects,
dehydration, lowers sugar and
potassium levels, weakness,
fatigue, diarrhea, kidney issues,
hypersensitivity reactions, and
irregular heartbeat [78,79].
5. Ganja
(Cannabis Sativa L.)
Various contaminants because of
the plant’s biosorbent properties.
These include heavy metals like
cadmium, copper lead and
mercury [80,81], residual
chemical solvents, pesticides and
microbes like Aspergillus that
produce mycotoxins.
Chemical residues (pesticides).
Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, lowers blood
pressure, increased heart rate,
dizziness, light-headedness, and
mild psychoactive effects [82].
6. Guinea Hen Weed
(Petiveria alliacea L.)
Chemical residues (pesticides)
and microbes. Coumadin—a
blood thinner [83].
Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea, and
dizziness. Abortive and
hypoglycemic effects [83].
7. Moringa
(Moringa oleifera Lam.)
Various contaminants because of
the plant’s biosorbent properties.
These include heavy metals like
cadmium, copper lead and
mercury and microbes [84].
Chemical residues (pesticides)
Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, lowers blood
pressure and heart rate, fertility
interference, uterine
contractions [85].
8. Lignum Vitae
(Guaiacum officinale L.)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach.

Molecules 2021,26, 607 24 of 30
Table 3. Cont.
Plant Possible
Contaminants
Type of Medicinal
Preparation Side-Effects
9. Garlic (Allium sativum L.)
Chemical residues (pesticides).
Microbial contaminants [86] and
heavy metals like lead and
sulfites [87].
Decoction
Generally safe and negligible
side effects like bloating, nausea,
gas, upset stomach, bad breath
and body odor, vomiting,
diarrhea, heartburn,
mouth/throat burn [88].
10. Sorrell
(Hibiscus sabdariffa L.)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
11.
“Search-mi-heart”
(Rhytidophyllum
tomentosum (L.) Mart.
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
12. Pepper elder
(Piper amalago L.)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
13.
McKatty Weed/Marigold
(Bidens reptans (L.) G.Don
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
14. Chany Root
(Smilax balbisiana Kunth)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
15. Lemongrass/Fevergrass
(Cymbopogen citratus L.)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
16. Cerassee
(Momordica charantia L.)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
17. Soursop
(Annona muricata L.)
Chemical residues (pesticides)
and microbes.
Annonacin, an acetogenin that is
toxic to the nervous system [89].
Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, movement
disorders, sensation issues [90].
Consumption = Increased risk of
atypical parkinsonism
development [89].
18. Leaf of life (Bryophyllum
pinnatum (Lam.) Oken
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
19. Dogblood
(Rivina humilis L.)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
20.
Lime Leaf Tea
(Citrus aurantiifolia
(Christm.)
Swingle
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.
21. Jack-in-the-bush
(Eupatorium odoratum L.)
Chemical residues (pesticides)
and microbes. Decoction
Generally safe and negligible
side effects like bloating, nausea,
upset stomach, diarrhea,
and dizziness.

Molecules 2021,26, 607 25 of 30
12. Economic Analysis of Phytomedicines Related to Antiviral Drugs
According to a report titled “Anti-Viral Drug Therapy Global Market Report 2020–30:
COVID-19 Implications and Growth” by Research and Markets, the global antiviral drug
therapy market is expected to grow from USD 52.2 billion in 2019 to about USD 59.9 billion
in 2020 [
91
]. This is primarily due to the increase in demand for antiviral drugs for the
treatment of COVID-19. The market is expected to stabilize and reach USD 62.6 billion at a
compound annual growth rate (CAGR) of 4.6% through 2023 [91].
According to a report titled “Global Herbal Medicine Market Research Report—Forecast To
2023” by Market Research Future, the herbal medicine market is expected to reach USD
111 billion by the end of 2023 [
91
]. The global herbal medicine market is projected to grow
at a compound annual growth rate (CAGR) of ~7.2 % from 2017 to 2023 [92].
Economic Analysis of Phytomedicines in the Caribbean
Jamaica’s medicinal cannabis market value is estimated to be around USD 300–400 mil-
lion. In consideration of the wide diversity of other Jamaican medicinal plants, this value
could increase three-fold. Table 4directly below lists some valuable patents on Jamaican
medicinal plants.
Table 4. Examples of patents on Jamaican Medicinal Plants.
Therapeutic Window/Benefits of Flavonoids Plant Patent Number Reference
1.
Therapeutic agents containing cannabis
flavonoid derivatives
targeting kinases, sirtuins and oncogenic agents for the
treatment of cancers.
Cannabis sativa L. US20180098961A1 [93]
2.
Agent containing flavonoid derivatives for treating
cancer and
inflammation.
Cannabis sativa L. US20170360744A1 [94]
3.
Therapeutic agents containing cannabis flavonoid
derivative for
ocular disorders.
Cannabis sativa L. US10278950B2 [95]
4.
Therapeutic agents containing cannabis flavonoid
derivatives for the prevention and treatment of
neurodegenerative disorders.
Cannabis sativa L. US10751320B2 [96]
5.
Pi 4-kinase inhibitor as a therapeutic for viral
hepatitis, cancer,
malaria. autoimmune disorders and inflammation, and a
radiosensitizer and immunosuppressant.
Vernonia acuminata
DC. WO2018022868A1 [97]
6.
Therapeutic antiviral agents containing
cannabis cannabinoid
derivatives.
Cannabis sativa L. US20180214389A1 [98]
7.
Methods for inhibiting HIV-1 activity by inhibitory
mechanisms of extracts of
Guaiacum officinale L. (Zygophyllaceae)
Guaiacum officinale L. US9814747B2 [99]
8.
Therapeutic potential of dibenzyl trisulfide Isolated from
Petiveria alliacea L. (Guinea Hen Weed, Anamu) Petiveria alliacea L. Patent pending [45,100]
13. Conclusions and Future Prospects
As estimated by the World Health Organization (WHO), over 65% of the world popu-
lation utilize botanical preparations as medicine [
1
]. Natural alternatives are increasingly
gaining attention because of greater accessibility to medicinal plants, and the possibility
that they may have fewer and less adverse side-effects than synthetic drugs. This makes
natural alternatives more desirable as novel drug therapies. Thousands of plant species still
remain to be screened for their bioactivity. Only approximately 15% of some 250,000 species
of higher plants have been studied for their pharmaceutical potential [
4
]. Only 5% of these
plants had one or more forms of biological activity [
101
]. This means that there is an enor-

Molecules 2021,26, 607 26 of 30
mous, untapped potential for the development of a myriad of plant-based therapeutics and
pharmaceutical-grade proteins likes vaccines, hormones, antibodies and cytokines [102].
Jamaica is home to many established medicinal plants such as ginger, garlic, medina,
ganja, cerasee, ball moss and fever grass [
103
]. This makes the island particularly welcom-
ing for rigorous scientific research on the medicinal value of plants and the development
of phytomedicine thereof. This could have great economic and medicinal implications,
not only for Jamaica, but for the region. Our traditional use of these medicinal plants
in Jamaica can be attributed to the passing of knowledge from traditional Asian and
African medicine.
Jamaica’s enormous “ethnopharmacopoeia” in addition to rigorous community-driven
scientific data sharing through globalization could potentially expedite natural-product
development, lower the cost to purchase natural-products and the cost for commercializa-
tion of natural-based drugs, and increase the availability of natural-based pharmaceuticals.
Despite the increasing scientific evidence supporting the medicinal value of plants native
to and cultivated in Jamaica, commercialization of natural-products derived from these
efforts is limited by factors including inadequate testing systems, uncertain regulatory
landscapes in natural-product biomedical research, manufacturing practices, commercial-
ization, licensing and intellectual property. As a result, the lack of a rational approach to a
creating a sustainable natural-product pharmaceutical industry has been limited.
Modern research around the world should now focus on the pharmacological activ-
ities of the phytochemicals and mapping their genomes and transcriptomes to produce
target drugs. There is a need for more systematic botanical, physicochemical and chem-
ical analyses of thousands of potential medicinal plants. Further research is required to
determine the efficacy, dosage standards, optimum extraction methods/solvents, cyto-
toxicity/hepatoxicity, pharmacokinetics, molecular mechanisms of action, phytoantiviral
screening methods, and drug interactions for many phytoantivirals.
Creating and using universal sets of primers, databases and standards to catalogue
species by research groups all around the world, would increase the level of reliability
and the number of species available for study (which has reached the greatest level ever
achieved by the scientific community) while also making it possible to identify an ever-
growing number of species [
104
]. In addition, a greater awareness of efficacies, toxicities
and drug-to-drug interactions of traditional herbal medicines is required. Most impor-
tantly, before these plant-based drugs can be incorporated into conventional medicine,
more randomized, double-blind, placebo-controlled clinical trials are need on a larger
scale. Data generated from such experiments should also be logged in a universal, open-
access database. Countries dependent on traditional, synthetic medicine, need to re-shift
focus to programs aimed at systematically studying the bioactive compounds from plants,
and synthesizing new drugs from compounds.
Author Contributions:
Conceptualization: H.L., and B.S.; writing, review and editing: H.L., B.S.,
J.B., N.T., E.F. and W.N. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement:
Not applicable. This study did not involve humans or animals.
Informed Consent Statement: Not applicable. This study did not involve humans or animals.
Data Availability Statement:
Data sharing is not applicable to this article. No new data were created
or analyzed in this study.
Conflicts of Interest:
Authors H.L. and N.T. are employees of Vilotos and Flavocure and both
companies have commercial interest in Caflanone. The other authors declare no conflict of interest.
Neither Vilotos nor Flavocure took part in the study or experience.

Molecules 2021,26, 607 27 of 30
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