NewBioWorld A Journal of Alumni Association of Biotechnology (2021) 3(2):13-21
REVIEW ARTICLE
Combating SARS-CoV-2 and other
Infectious Diseases with Enhanced Immunity by Herbs and Spices, and Preventing
its Community Transfer via Ancient Indian Traditions and Culture
Nisha Gupta1, Esmil
Beliya1,2, Shubhra Tiwari1, Jai Shankar Paul1*,
Shailesh Kumar Jadhav1
1School of Studies in Biotechnology, Pt. Ravishankar
Shukla University, Raipur, 492 010 (CG), India
2Department of Botany, Govt. College, Bichhua, Chhindwara,
480 111 (MP), India
*Corresponding author: jaishankar_paul@yahoo.com
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ARTICLE
INFORMATION
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ABSTRACT
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India and
several other countries are facing the biggest threat to survival due to a
novel pandemic called Coronavirus and diseases (COVID-19) which was
originated from Wuhan in China in the year 2019. This coronavirus belongs to
the group of respiratory viruses (SARS-CoV-2). Its mode of transmission is
through respiratory droplets released from the mouth of an infected person
while sneezing or coughing. This outbreak has forced to shut down several
countries to minimize its community spread. Due to this current lockdown,
affected countries are facing several challenges viz. health issues,
economical pressure, educational, religious, and social affairs etc. As it
can be seen that the world’s biggest pandemic i.e., COVID-19 is spreading at
a very high rate and has taken away the lives of innumerable people worldwide
since the initial days of its occurrence. Therefore, it is necessary to
prevent its social spread to save the lives of many people all over the
world. This manuscript deals with several essential ethnopharmacological
herbs and spices which can be incorporated in diet to prevent infectious
diseases. Also, it will revive the role of ancient Indian tradition, cultures
and beliefs in preventing the spread of infectious diseases and thereby
decreasing the chances of its occurrence.
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Keywords:
COVID-19; Ethnopharmacology; Indian tradition;
Infectious diseases; Spices and herbs
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Introduction
Currently, all over the world including India is suffering from the
world’s biggest viral outbreak of the year 2019 namely Coronavirus and disease
i.e., COVID-19. Coronavirus was firstly originated in Wuhan city, Hubei
Province, China in December 2019, the epicentre of this outbreak (Bahadur et
al. 2020; Muthusami and Saritha 2020; Rothana and Byrareddy 2020). Thousands of
people died globally in a very short period because of being suffering from
deadly COVID-19 and it is still in its fatal stages (Liu et al. 2020).
This deadly Coronavirus has been named as
the biggest pandemic of the year or “Public Health Emergency of International
Concern (PHEIC)” by the World health organization (WHO) (Kalteh and Rajabi
2020). It has led to a massive loss to mankind all over the world including
China, Italy, Spain, Germany, France, Iran, Japan, Switzerland, Canada, USA and
India etc., and it is still in progress. With each passing day, this viral
pandemic is getting worst and out of control. All suffering countries including
India has been lockdown to prevent the chances of community transfer for
several months and infected people are recommended to live in quarantine
ranging from a few days to a month after their treatments. Central, as well as
state governments of infected countries, are taking necessary precautions to
break this coronavirus chain. Timely guidelines have been provided to normal
people for awareness regarding preventive measures.
COVID-19 tracker website (www.mohfw.gov.in) is available in India to
provide information about the total number of coronavirus positive cases and
the total number of death and also to provide some preventative measures.
Instead of having several medicinal therapies and costly treatments to cure
such infections, the major focus should be given to disease prevention because
it has been truly said that prevention is better than cure.
India is
a nation of various cultures, traditions, civilizations, religions and
languages (Worthington and Gogne 2011). It has so many old sayings, remedies,
cultures and beliefs since ancient time for the prevention of various
infectious diseases. There are scientific reports and findings which proves the
positive impact of Indian tradition in avoiding chances of getting infected.
The current study will emphasize on some immunomodulating food items including
medicinal herbs and spices which serves an efficient alternative for anti-viral
therapeutics. This allows them to use as a potential herbal medicine for
fighting infectious diseases including COVID-19 by enhancing our immunity when
incorporated in our regular diet.
Coronavirus: A novel
and fatal respiratory virus
The large,
positive-sense single-stranded RNA (26-32 kb) Coronaviruses belong to family Coronaviridae
in order Nidovirales, the causal organism of the most common severe acute
respiratory syndrome (SARS-CoV) and naturally resides in birds and mammals (Li
2016; Ghosh et al. 2018; Bahadur et al. 2020; Parakevis et al. 2020). It has
four genera including Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and
Deltacoronavirus (Sivabakya and Srinivas 2020). Out of them, alpha and
betacoronaviruses infect mammals, gammacoronaviruses infect birds, and
deltacoronaviruses infect both mammals and birds (Li 2016). Coronavirus
consists of four structural layers that is made up of protein viz. spike
protein (S), membrane protein (M), envelope (E) and nucleocpsid protein (N)
from outside to inside (Fig. 1). A crown like appearance is given by the spike
protein. The most common symptoms of COVID-19 include fever, headache cough,
breathing difficulties, tiredness, mucus production, haemoptysis, diarrhoea,
and decrease in WBC count (Bahadur et al. 2020; Huang et al. 2020; Koenig 2020;
Rothana and Byrareddy 2020).
Fig. 1 Structure
of SARS-CoV-2
Life
cycle of Coronavirus
The life cycle of SARS-CoV-2 begins when it
gains its entry into the host cell via cellular receptor namely
Angiotensin-Converting Enzyme 2 (ACE2) which cause some conformational changes
in the spike protein (Fig. 2). A protease namely cathepsin (TMPRRS2) along with
other proteases digest the spike protein and then facilitates the binding of
the host cell membrane with the viral membrane which ultimately helps the virus
to enter the host cell via endosomal pathway (Fehr and Perlman 2015). After
entry into the host cell, the virus releases its ssRNA into the host cytosol
for the translation of the replicase gene which encodes two large ORFs, rep1a
and rep1b. The virus operates a slippery sequence (5′-UUUAAAC-3′) and an RNA
pseudoknot that results in ribosomal frameshifting from the rep1a reading frame
into the rep1b ORF to express both rep1a and rep1ab. These ORFs are then
translated into two polyproteins, pp1a and pp1ab (largest). The polyproteins
pp1a encodes 11 non-structural proteins whereas pp1ab encodes 16 non-structural
proteins (Fehr and Perlman 2015; Shereen et al. 2020). The above mentioned
polyproteins are then digested by viral proteases (papain-like proteases
(PLpro), and a serine protease, the main protease) to generate individual nsps.
Many of these individual non-structural proteins (nsp) gather to form a
replicase-transcriptase complex (RTC) to transcribe and translate subgenomic
RNAs to form all the viral components which afterward assembled into virions in
the ER and Golgi and then transported via vesicles and then released out of the
cell via exocytosis (Shereen et al. 2020).
Factors
responsible for COVID-19 transmission
There are various intrinsic aspects as well as
extrinsic aspects which influences the spread of infectious diseases from one
person to another (Fig. 3). Furthermore, climate change has also a major impact
on the spread of various infectious diseases and on human health (Xun et al.
2010; Parry et al. 2019).
Indian
diet, beliefs, traditions and cultures in alleviating COVID-19 infection
All over the world, infectious diseases are
the cause of death of about 25% of people per annum (Kapiriri and Ross 2018).
India is a nation of various cultures, traditions, civilizations, religions and
languages (Worthington and Gogne 2011). It has so many old sayings, remedies,
cultures and beliefs since ancient time for the prevention of various
infectious diseases. There are scientific reports and findings which proves the
positive impact of Indian tradition in avoiding chances of getting infected.
Tradition
of Vegetarianism
In order to
prevent various zoonotic diseases, nutrient-rich diet is an essential factor
which needs to be taken care of (Gicevic et al. 2019). The origination of
COVID-19 is due to the consumption of wild animals which helped in the zoonotic
transmission of virus directly from animals to human beings. After unveiling
the cause of coronavirus, people are becoming so conscious about their diet.
The most effective way to prevent zoonotic infection from origination is to
avoid non-vegetarian diet. This outbreak has once again encouraged vegetarian
diet which comprises of various nutritious foods which are enriched with high
fiber, vitamins, minerals, protein etc. like fruits, green vegetables including
spinach (palak), green coriander, drumstick (Moringa oleifera), broccoli, mint,
basil leaves, curry leaves, green chili, mandukparni (Centella asiatica),
brahmi (Bacopa monnieri), grains, jaggery, honey and unprocessed food.
Fermented foods
and beverages are also included in regular diet (Ray et al. 2016). Traditional
fermented food preparation is one of the oldest biotechnological processes in
which microorganisms play a crucial role by improving the nutritional
characteristics by allowing the easier digestion of carbohydrate, enrich body
with essential amino acids, vitamins. This amazing benefit of fermented food is
that it helps to maintain normal microflora of the gut which is obligatory in
avoiding various diseases and also to maintain body homeostasis of the host
(Ray et al. 2016). Fermented rice based food products such as idli, dhokla,
uttapam, dosa and vada etc. helps to fulfill various ailments related to
nutrient deprivation (Tamang 2020). For preventing microbial contamination in
cooked food items, appropriate hygiene is maintained while cooking these food
items to prevent microbial contamination and thus preventing the occurrence of
diseases.
Furthermore,
drinking water in a metal vessel especially made up of copper has been
scientifically proven that it has so many health benefits like the water stored
in a copper vessel for overnight is microorganism free and will enrich our
health with stronger immunity, better digestion, and will also help to balance
our body fluid’s pH.
Ritual of
eating curd
Consuming curd (Dahi) in regular diet rich our
gut with healthy bacteria including Lactic acid bacteria (LAB). Furthermore,
curd is rich in vitamins, minerals and also has probiotic properties. Hence,
curd is highly recommended for patients suffering from diseases and disorders
like allergies, atherosclerosis, and gastrointestinal disorders like
constipation, indigestion and diarrhoea etc. (Khedkar et al. 2016).
Fig. 2 Life cycle of Coronavirus
Fig. 3 Factors responsible for
COVID-19 and other infectious disease transmission
Anti-viral
effects of some spices and herbs
Spices as well as herbs are reservoir of
various bioactive components which have numerous pharmacological roles (Table
1). They have been used in different forms like oral herbal formulations
(decoction or kadha), aqueous and solvent extracts, and in supplementation with
various allopathic drugs to either enhance their efficacies or to neutralize
the side-effects generated by that drug up to some extent. Several
precautionary measures are provided by Ministry of Ayush
(https://www.ayush.gov.in/) for preventing COVID-19 infection. The guidelines
include the herbal decoction (kadha) made up of various herbs and spices like
holy basil, cinnamon, black pepper, cumin, turmeric, ginger and coriander, and
black paper etc. This was accompanied by oil pulling therapy to clarify nasal
passage, various pranayama, meditation and consumption of golden milk twice a
day is highly recommended.
Magical
herbs and spices in kitchen
Kitchen is full of medicinal herbs which is
widely used in cooking like turmeric (Curcuma longa), ginger (Zingiber
officinale), garlic (Allium sativum), onion (Allium cepa), black pepper (kali
mirch), fennel seeds (saunf), fenugreek (methi), cumin (jeera), ajwain
(Trachyspermum ammi), sesame seed or til (Sesamum indicum), flax seed or alsi
(Linum usitatissimum), mustard seeds or sarso (Brassica nigra), clove (laung),
cardamom (elaichi), asafoetida (hing), tezpata or Indian bay leaf (Cinnamomum
tamala), cinnamon or dalchini (Cinnamomum verum), nutmeg (jayphal), coriander
(dhania) and saffron (kesar) etc. (Fig. 4). All these herbs and spices helps to
cure various human ailments like the common cold, flu, cough, arthritis,
headache, fever, bodyache etc. by boosting immune power in the body which makes
it capable for fighting and preventing various infectious diseases. A visitor
from China namely I-Tsing visited India and studied the various traditional and
cultural practices of people living there and described it in his book called
“Bharat ki Yatra” (Santram). He studied that the people of India uses various
medicinal plants to cure human diseases.
Fig. 4 Various herbs and spices used in Indian kitchen
Immunomodulating
food items
It is mandatory to fulfill all the nutritional
requirement of an individual to stay fit and disease-free. There are varieties
of food items which are the reservoir of vitamins, minerals essential amino
acids, and micronutrients which help to modulate our immune system and thereby
decreasing the chances of infection (Table 1).
The Hindu
ritual of yagnas, pooja and havan (traditional fumigation technique)
In ancient time people use to do various kinds
of pujas and yagnas by sublimating havansamagri which comprises of a mixture of
wood like neem stems (Azadirachta indica), chandan (Santalum album), Arjun
(Terminalia arjuna), goolar (Ficus racemosa) etc. and dried medicinal herbs
like haldi (Curcuma longa), betel nut, betel leaves, dhoop etc. which is mixed
with camphor and ghee for burning in fire (Fig. 5) to purify their surroundings
by killing microorganisms and to attain the peace which is also described in
Rigveda, the most ancient Indian compilation of knowledge. Havan is a type of
disinfection technique which can be easily applied to purify and sterilize
their surroundings.
Table
1 Immune system modulating food items which
ultimately helps in fighting infection
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S. No.
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Food item
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Type of immune
modulating activity
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References
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1.
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Syzygium aromaticum
(clove)
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Inhibits NF-κB activation and also Inhibits viral
DNA polymerase and hence synthesis of HSV-1 and HSV-2.
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El-SaberBatiha et al.
2020
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2.
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Curcuma longa
(turmeric)
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Inhibiting NF-κB signaling pathway and improves
pulmonary inflammation caused by influenza virus.
Inhibits infection causing capacity of ZIKV and
CHIKV.
As curcumin is lipophilic it can alter membrane
fluidity and thereby decreasing binding capacity of virus to receptor.
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Mounce et al. 2017; Xu
and Liu 2017
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3.
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Allium cepa
(onion)
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Act as a virus (hepatitis virus, poliovirus,
influenza virus, HIV virus, and SARS virus) inhibitor via preventing viral
replication by blocking its receptor binding and also prevents virus assembly
for the formation of new viruses.
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Sharma 2019
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4.
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Allium sativum
(garlic)
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Effecting in treating several viruses such as Rhinoviruses,
HIV virus, HSV, viral pneumonia and rotaviruses via stopping virus
multiplication, prevents the release of TNF-α, IL-6, blocks NF-κB signaling.
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Sharma
2019
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5.
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Zingiber officinale
(ginger)
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Inhibit viral protein (G and F) of HRSV and hence
prevent them from attachment and entering in host body. It also stimulates IFN-β secretion.
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San Chang et al. 2013
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6.
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Litchi
(Litchi chinensis)
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Good anti-oxidative property by killing superoxide
radicals, anti-tumorous by up-regulating apoptotic genes like Bax protein and
caspase-3, cell-cycle regulating genes (CDK-inhibitors) and down-regulating
the signaling pathway associated with cancerous cell.
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Emanuele et al. 2017
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7.
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Kiwifruit
(Actinidia chinensis)
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Antimicrobial activity by releasing β-defensins and
promoting opsonization of bacteria, enhance IFN-γ and NK
cell activity, cytokine secretion by upregulation of IL-2 by binding of
polyphenols of kiwifruit to γδ TCR.
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Skinner et al. 2013
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8.
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Dates fruit
(Phoenix dactylifera)
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Anti-inflammatory properties by suppressing NF-κB,
modulate cytokine secretion, prevents lipid peroxidation by inhibiting COX1
& COX2, act as an antioxidant by damaging free radical and thereby
preventing disease progression.
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Rahmani et al. 2014
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9.
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Dairy products
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Resist
infection by improved gut health via enhanced amount of B cells, NK cells,
APC, CD4+, CD25+, and CD8+, CD25+
in peripheral blood cells.
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Wu et al. 2019
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10.
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Palak
(Spinacia oleracea)
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Act as a scavenger of free radicals, inhibit COX-2,
down-regulate action of NF-κB, prevents association of cyclin A and CDK-2 by enhancing CDK
inhibitor (p21cip1) during G1/S cell cycle progression which prevents
phosphorylation of Rb gene and thereby no synthesis of E2F-1 factor and hence
promote cell cycle arrest in cancerous cell.
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Roberts and Moreau 2016
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11.
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Jaggery
(gur)
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Act as a lung cleanser by translocation of the dust,
coal and smoke particles from lungs in occupational labours,
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Sahu and Saxena 1994
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12.
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Tulsi
(Ocimum
sanctum)
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Immunomodulatory action by up-regulating secretion
of IL-2, IFN-γ and TNF-α and down-regulating IL-1β which is responsible for
invasiveness of tumor cells, inhibit NF-κB pathway and hence
act as an anti-inflammatory herb.
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Hemalatha et al. 2011
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13.
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Gotu
Kola
(Centella
asiatica)
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High anti-oxidative property, inhibit AChE levels
and hence suppressing Alzheimer’s disease and inflammation
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Hafiz et al. 2020
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14.
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Honey
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Antibacterial property, stimulate wound healing by
suppressing reactive oxygen intermediate and hence act as an
anti-inflammatory agent, stimulate synthesis of cytokine TNF-α, IL-1β, IL-6 by blood
monocytes.
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McLoone et al. 2016
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Note: Nuclear factor kappa B ( NF-κB ), SARS- Severe Acute Respiratory Syndrome
,HSV- Herpes Simplex Virus, ZIKV- Zika
virus, CHIKV- Chikanguniya virus, HIV- Human immunodeficiency syndrome, HRSV-
Human Respiratory Syncytial Virus, NK-Natural killer,
IL-2 Interleukin-2, TCR- T- cell receptor, COX-cyclooxygenase enzymes,
AChE- acetylcholinesterase
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Fig. 5 Various
things used in havans and yagnas (A- dhoop, B- havansamagri, C- camphor)
Fig. 6 Lifestyle
changes for the prevention of community spread of COVID-19
Behavioral
roles of Indian cultures and traditions in preventing the community transfer of
COVID-19
There are various lifestyle measures since
ancient time which can be so helpful in breaking the chain of spread of
infectious diseases (Fig. 6). Several influential remedies for preventing the
spread of infectious diseases including COVID-19 have been incorporated in this
manuscript.
The
Indian tradition of touchless greetings
Corona outbreak has given rise to a new
etiquette i.e., touchless greetings ‘Namaste’ which is very common in Indian
culture and tradition. Indian culture has a habit of folding of their hands
together for greeting, or in prayer, or as a symbol of respect for someone,
which indirectly taught us to maintain the hand hygiene rituals (Khuan et al.
2018).It has revived the ancient Indian tradition to do namaste instead of
shaking hands which directly provides a medium for the microbial transmission
which are responsible for various diseases. Hand hygiene should be performed
frequently to avoid colonization of microorganisms in our body for example,
washing of hands is necessary before having anything in our mouth to avoid
entry of pathogens inside the body (Allegranzi and Pittet 2009; Khuan et al.
2018).
Tradition
of personal hygiene
Lives
of thousands of human have gone and countries are suffering from financial
losses because of the most common healthcare-associated infections (HAIs).
Prevention of HAIs can be done through proper hand hygiene which also reduces the
rate of mortality and cost of medical facilities (Khuan et al. 2018). We should
always wash our hands and feet just before entering our homes after coming from
our workplace to prevent microorganisms from getting inside the house. We
should wash our hands properly whenever we are having our meal. It is also
mandatory to wash our hands after changing diapers of children in order to
avoid infection arises due to faecal matter (Curtis et al. 2003). A minimum of
20-30 seconds of hand wash should be done with either soap or water or with
alcohol-based sanitizers helps in killing germs.
The
Indian tradition of fasting
Fasting
or the intermittent fasting is being followed since ancient times. In fasting,
individual do not eat anything for a definite time interval. Fasting duration
of an organism allows them to repair their biological machinery and to withdraw
energy more efficiently when food is consumed (Longo and Panda 2016). In Indian
culture, fasting is not a compulsion, but is generally advised to achieve peace
and purity of mind. Fasting has been scientifically proven by various
researchers for contributing to a range of physiological functions such as
autophagy of cells (‘self-eating’) which is increased due to fasting which was
proven by Yoshinori Ohsumi of Japan who Wins Nobel Prize for the same,
scientific reports and findings also supports fasting. I-Tsing also reported
the importance of fasting for human being. He reported that continuous fasting
for some days (usually 4-5 days) is beneficial in treating diseases. Various
scientists have also proved the positive impact of fasting by conducting
experiments in various animal models and also in cell lines and concluded that
fasting can inhibit cancer cells and ageing, autophagy, eliminating pathogens,
weight loss, improved blood sugar levels and brain functions, and cleansing of
cells from insides etc.
Tradition
of ‘Pranayama’, ‘Surya namaskara’ and meditation
The people across the world follow so many
health and fitness-related ritual especially in the morning to keep their
physical and mental health free from diseases, stress and anxiety. They perform
a different kind of yoga, asana and various exercises since ancient times.
I-Tsing also described the health benefit of physical activities like walking,
jogging. Performing the ‘Surya Namaskar’ (Sun Salutation) every morning gives
so many health benefits like it reduces the tension from body and mind,
rejuvenates the physical and mental body, improves blood circulation, regulates
breathing pattern and enriches our central nervous system. The scientific
explanation behind this is that by doing pranayama and yoga body heals itself
through various machinery and gives us so many advantages like it lowers the
blood pressure and reduces the risk of cardiovascular diseases, maintains
healthy body weight, improves the physical state of cancer patients, eliminates
stress and anxiety from the mind, brings peace and calmness to our soul and
strengthens our lungs and hence improves respiration etc. (Sengupta 2012).
Tradition
related to pregnant ladies and with the new-born
There is one normal nutrition-related
conviction that during pregnancy ‘hot’ nourishments is destructive and 'cold'
food sources are advantageous. The possible explanation behind this is that
during pregnancy there is a rise in the overall internal body temperature so,
for normalizing purposes, it is advised to eat cold food instead of hot food
(Choudhry 1997). Additionally, hot nourishments are supported during the most
last month of pregnancy to ease labour pain.
Secondly, quarantine of new mother and child
for few days from gathering places just after the delivery, to prevent them
from expose to outer contamination and which reduce the chances of infection to
new baby and mother. The mother after delivery prefers to live at her parental
house to get complete rest and nutritional care. After the delivery, the new
mother has been massaged with a special kind of oil by a midwife to relieve her
body pain and the main focus is given to her diet. Her diet includes high
protein and vitamins enriched foods like dry fruits, green vegetables, fruits,
milk and ghee as it is believed that ghee enhances the quality of breast milk.
Indian
ritual of bathing after funeral (sanitization of whole body) after funeral
People after attending the funeral follows a
habit of bathing to wash off the whole microorganism from their body which
prevents all those microorganisms from entering into the houses. A scientific
explanation behind this is that funeral places are treated as contaminated
spot, since all individuals, regardless of their wellbeing condition, are
permitted to visit in the funeral. Because of that, the air around it is fully
contaminated with infectious germs. Also, when an individual is dead, their
body becomes unresponsive to pathogens and as a result body starts decaying.
The individuals who attend funeral come in direct contact with the dead body
and henceforth directly to the microorganisms. Chanakya, one of the world's
most popular researchers, clarifies that it is significant for people to wash
or tidy up themselves whenever they are attending the funeral.
Conclusion
The best way to stay fit and healthy is to
prevent infectious diseases as much as possible. There are so many remedies or
changes which can be incorporated in daily life through which one can remain
fit and fine without costing a penny. All these dealings regarding various
herbs and spices or various changes in lifestyle have numerous scientific
evidences given by many of the researchers, scientist as well as biologists.
This manuscript has dealt with all those measures through which we can prevent
the spread of fatal infectious diseases which cause massive loss to mankind.
This manuscript may encourage the people living in worldwide for a little change
in their lifestyle to live healthy and disease-free. The study strongly
supports that herbs and spices have tremendous anti-viral properties which
allows them to use as a potential herbal medicine for fighting infectious
diseases by enhancing our immunity when incorporated in our regular diet to
inhibit viral diseases like COVID-19 and other infectious diseases. Also Indian
cultures and traditions play a major role in preventing the social spread of
COVID-19 and other infectious diseases.
Acknowledgement
The authors acknowledge School of Studies in
Biotechnology, Pt. Ravishankar Shukla University Raipur, Chhattisgarh for
providing facilities to conduct this study. Authors also acknowledge Department
of Biotechnology (DBT), Government of India, New Delhi, for providing financial
support as DBT-JRF fellowship to author Nisha Gupta during the tenure of this
study (Sanction no. DBTHRDPMU/JRF/BET-20/I/2020/AL/319). Authors also
acknowledge DST-FIST for financial support to School of Studies in
Biotechnology Pt. RSU Raipur, Chhattisgarh (Sanction No. 2384/IFD/2014-15,
dated 31.07.2014).
Funding
information not applicable.
Compliance
with Ethical Standards
Conflict
of interest All authors declare that they have no any conflicts of interest in any
part of this study.
Ethical
approval This article does not contain any studies with human and animal
participants performed by any of the authors.
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