Spirulina Extract Enhances T-Cell Responses Targeting Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Potential Drug Candidate for Treatment of COVID 19

Abstract

Globally, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) killed more than 323k
people and trimmed the economic growth significantly. Vaccine development is not soon and people may
require living with the SARS-CoV-2 virus. T helper cells target the spike protein of SARS-CoV-2. And a strong
T cell response is directly proportional to the rate of SARS-CoV-2 suppression. Spirulina augmented
interferon-gamma (IFN ) & Natural Killer (NK) cell cytotoxicity in humans. Spirulina was effective in inhibiting
several viral replications like HIV-1 and potentially induced IFN in healthy volunteers. Immunity is the ultimate
protective shield combating with various infectious diseases including COVID-19. A nutrient supplement
Spirulina being an effective immunomodulator showed promising results in proliferating cell-mediated immunity
and activation of T-cells. Spirulina extract degrades histone deacetylases responsible for the inflammatory gene
expression. Spirulina is associated with a wide range of adverse events and in few people it may be fatal.
So, people with allergies, autoimmune disorders and other underlying medical conditions should consult
healthcare professional before consuming. Pure Spirulina extract is safe (not regulated by the US FDA) and a
potential drug candidate in combating with the SARS CoV-2. This review recommends well-controlled,
randomized clinical trials to confirm the effectiveness of Spirulina in inhibition and proliferation of the novel
virus in the human body

Full text

American-Eurasian Journal of Toxicological Sciences 12 (1): 08-13, 2020
ISSN 2079-2050
© IDOSI Publications, 2020
DOI: 10.5829/idosi.aejts.2020.08.13
Corresponding Author: Peter Pothula, Beside Arts College, Proddatur, India-516360.
8
Spirulina Extract Enhances T-Cell Responses Targeting Spike Protein of
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2):
A Potential Drug Candidate for Treatment of COVID 19
P. Peter
Beside Arts College, Proddatur, India-516360
Abstract: Globally, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) killed more than 323k
people and trimmed the economic growth significantly. Vaccine development is not soon and people may
require living with the SARS-CoV-2 virus. T helper cells target the spike protein of SARS-CoV-2. And a strong
T cell response is directly proportional to the rate of SARS-CoV-2 suppression. Spirulina augmented
interferon-gamma (IFN ) & Natural Killer (NK) cell cytotoxicity in humans. Spirulina was effective in inhibiting
several viral replications like HIV-1 and potentially induced IFN in healthy volunteers. Immunity is the ultimate
protective shield combating with various infectious diseases including COVID-19. A nutrient supplement
Spirulina being an effective immunomodulator showed promising results in proliferating cell-mediated immunity
and activation of T-cells. Spirulina extract degrades histone deacetylases responsible for the inflammatory gene
expression. Spirulina is associated with a wide range of adverse events and in few people it may be fatal.
So, people with allergies, autoimmune disorders and other underlying medical conditions should consult
healthcare professional before consuming. Pure Spirulina extract is safe (not regulated by the US FDA) and a
potential drug candidate in combating with the SARS CoV-2. This review recommends well-controlled,
randomized clinical trials to confirm the effectiveness of Spirulina in inhibition and proliferation of the novel
virus in the human body.
Key words: Cell-Mediated Immune Response Inhibition of Viral Replication Cytokine Storm Cytotoxic
Potential Stimulation of NK Cells
INTRODUCTION is coming down. Except for a few countries like South
The damage caused by the COVID 19 has been was not successful in many countries. As the economy is
considered as the world war 3. It killed more than 323k severely affected, industries closed, people have lost
people and the health crisis related economic impacts lead jobs, & hunger deaths in few countries rose, most of the
the risk and volatility in financial markets. Approximately, countries in the world decided to relax on restrictions in
13-32% fall in the global trade could be expected phases. Though the number of cases is increasing &
depending on the duration of this health crisis related WHO is a warning, countries have no options to handle
economic downturn [1]. this deepened economic crisis.
Many pharma companies and research & There are approved drugs (HCQ and remdesivir) to
development centers are putting ceaseless efforts in use in the emergency conditions and vaccine trials are
developing treatment drugs or a preventable vaccine. ongoing but chances are dim getting approved therapy
There were many theories, observations and assumptions for COVID 19 by the end of 2020. Then what is the
that evolved as the number of COVID 19 cases is alternate? Shall we live in the lockdown & wait until the
increasing. Many countries announced lockdown and vaccine comes in place?.
several countries shut down their normal life since March Many industrialists and scholars are saying that
2020. Despite several efforts, there was no change in the COVID 19 will not go naturally but people should live with
number of COVID 19 infections, the reproduction number it until vaccine development takes place. Interestingly,
Korea, New Zealand, Wuhan-China etc., the lockdown

Am-Euras. J. Toxicol. Sci., 12 (1): 08-13, 2020
9
Princeton university revealed that there is no effect of SARS-CoV-2 while suggesting as a potential drug
climate over the spread of the COVID 19 transmission, but candidate for COVID-19 care.
it may be a mitigating factor when the population becomes
resistant to the virus. As more immunity in the population RESULTS AND DISCUSSION
develops, the more we expect the increased sensitivity of
the virus to climate [2]. People with underlying medical Currently, vaccine development is focusing on
conditions and poor immunity are more sensitive to any immune response antibodies, the proteins produced by
infection including Severe Acute Respiratory Syndrome B-cells which ideally bound SARS-CoV-2 and prevent
Coronavirus 2 (SARS CoV-2) [3]. So, immunity in the them from entering cells. In contrast, T-cells prevent
human body is playing a crucial factor in protecting from infections in 2 ways; by activating B-cells into action
various infections. (T-helper cells) and destroying the infected cells (T-killer
The natural development of immunity to a pathogen cells). The severity of infection is inversely proportional
is a multi-step process that usually occurs in 1-2 weeks to the strength of T cell responses.
after infection. A viral infection triggers a non-specific Immunologists, Shane Crotty and Alessandro Sette
response within the human body producing macrophages at the La Jolla Institute for Immunology portrayed that
(ö), neutrophils and dendritic cells which delays the specific viral protein particles would provoke strong T cell
progression of the virus progression and further stopping responses. In a study, 15 out of 18 COVID patients
disease symptoms. This non-specific response is an reported T helper cells targeting the spike protein of
adaptive response, where antibodies (immunoglobulins) SARS-CoV-2 [6]. From the results, it is obvious that a
are produced and directly bind to the surface of the virus strong T cell response will suppress SARS-CoV-2
[4]. People are ready to wear masks, maintain social infection further arresting its proliferation. Before these
distance and all guidance to avoid SARS CoV-2 infection, results come into the limelight, it was unclear whether T
however, most of the population trying differently to cells eliminate SARS-CoV-2 or event whether they
develop or enhance immunity internally so that accidental provoke the immune system. According to Crotty, the
contact with the virus will not succumb them to the SARS results were encouraging as T helper cell responses
CoV-2 infection. against SARS-CoV-2 were well established [5].
Spirulina can be consumed as a healthy food because In a study conducted at UC Davis [7], immunologists
of its rich nutritional qualities. Spirulina is not regulated collected blood samples from 12 healthy volunteers
by the United States Food and Drug Administration and separated peripheral blood mononuclear cells
(US FDA) however, after reviewing a petition to consider (PBMC) including macrophages, monocytes and
Spirulina extract as a coloring agent in chewing gums and lymphocytes (B & T cells). Spirulina potentially induced
candies, concluded as safe [5]. Spirulina as a dietary interferon-gamma (IFN ) and moderately induced
supplement can be recommended at doses of 3 and 4.5 interleukin-4 (IL-4) and interleukin beta (IL-1 ) after
grams/day [6]. Several human & animal studies showed 72 hours of incubation.
that Spirulina is an effective immunomodulator and can Replication of Human Immunodeficiency Virus- 1
influence the activation of immune cells. Colossal (HIV-1) replication in human-derived T cells and in PBMC
bibliography is available on nutritional & therapeutically was inhibited with Spirulina at a concentration of 5-10
applications of Spirulina. mg/ml. The study concluded that even a small
Through research, we are discovering just how concentration of Spirulina is enough to reduce viral
Spirulina strengthening the immune system and how it is replication, however larger amounts with >100 therapeutic
beneficial if added to our diet [6]. This present review index, would completely arrest its replication [8].
focusses on the immunomodulating activities of Spirulina A purified extract of Spirulina (calcium-spirulan)
providing innate protection against SARS-CoV-2 inhibited replication of HIV-1, herpes, human
infection. cytomegalovirus (HCMV), influenza A virus, mumps and
measles virus. The extracts proved to be safe for human
MATERIALS AND METHODS & monkey cells in cell culture 8.
Literature related to immunomodulating effects of augmentation of IFN & Natural Killer (NK) cell
Spirulina in animal & human models are reviewed. The cytotoxicity in humans when given with hot-water
review centered on the immunoproliferation effects of extract of Spirulina platensis [9]. They established
Spirulina extract on different viral infections including similar results in mice, however, IFN is poorly induced
In another study, authors demonstrated

Am-Euras. J. Toxicol. Sci., 12 (1): 08-13, 2020
10
in mice compared to humans [9]. These results endorse conducted by Crotte and Thiel provides substantial
the efficiency of Spirulina in inducing the immune system
in humans.
In a double-blind controlled study, it was elicited
that Spirulina extract may protect athletes from
deterioration of immunity caused due to strenuous
exercises and prevents [10]. The extract of Spirulina
platensis triggered a significant effect on the stimulation
of NK cells and their cytotoxic potential [11, 12]. A pilot
randomized; comparative clinical trial conducted in
Hepatitis C (HCV) patients showed a significant decrease
in the viral load in Spirulina treatment group [13].
In Baby Hamster Kidney cell cultures and in baby
mice, non-toxic doses of S. platensis (50 ug/ml) showed
reductions in the type O, A and SAT2 titers of foot and
mouth disease virus (FMDV) by 35.7%, 28.5% and 31%
respectively [14].
Between 1979 and 1998, several animal studies
majorly including mice have demonstrated enhanced
immune response after administration of Spirulina extract
[15-25].
From the above results, it is apparent that T cells
have a strong action against SARS-CoV-2, not only
suppressing the infected cell but also arresting its
proliferation. The results were certain that T cells are
active against various viruses like HIV-1.
In consolidation, a nutrient supplement Spirulina, an
effective immunomodulator showed promising results
in proliferating cell-mediated immunity and activation of
T-cells; both helper & killer cells. Spirulina extract in high
concentrations can inhibit & arrest viral replications
completely.
In both human and animal models, Spirulina
showed positive immunological results in acting
against various viruses like HIV-1, HCV, Influenza,
FMDV, Measles, Mumps, etc., So, there is no doubt that
Spirulina can strengthen our immune system and
provides good protection against various viral infections
including SARS-CoV-2. Viruses may show different
mechanism of actions, but the immune responses
exerted by the human body is the same against all viruses.
The strength of the immune response will decide the
chances of getting infected and showing symptoms of the
disease.
For ages, Spirulina has been a lifesaver and
considered a miraculous single-cell protein with many
therapeutic applications. Though, limited research was
conducted on Spirulina and its immunological effects
against SARS-CoV-2, the outcomes from the studies
evidence to the discussion.
The above investigations demand additional studies
to determine these effects in the patients consuming
Spirulina. The data is limited and no appropriate method
was used to interpret the results. Amazingly, even
secondary metabolites produced by Spirulina have
exhibited therapeutic applications [26].
Immunity plays a crucial role in determining the
health of a human being. A strong immune system can
keep human beings away from all infectious diseases and
viruses. In general, the preferential increase in IFN
production over IL-4 would shift the immune system to
mounting a cell-mediated immune response rather than a
humoral response. A cell-mediated response involves
activating T-cells and antibodies which work with
macrophages. The moderate increase in IL-1 secretion,
a cytokine that acts on almost every cell in the body to
promote inflammation, works to support the overall
immune response.
COVID-19 & Cytokine Storm: When a pathogen enters
into the human body, hyperactive immune system
sometimes may activate destructive overacted reaction
termed a cytokine storm [27]. Exaggerated immune cells
spread across and start attacking healthy cells; red blood
cells and white blood cells finally damaging the liver.
Blood vessels may become leaky accumulating fluid in the
lungs & blood clots may chock the flow of blood causing
shock, organ damage and finally death. From a study of
29 severe Covid 19 patients, Wuhan physicians reported
cytokine storm reporting high levels of the cytokines
(pro-inflammatory) IL-2R and IL-6. High levels of IL-6 may
be an early indicator for cytokine storm [27]. Another
team in Wuhan analyzed 150 patients and reported that
IL-6, C-Reactive Protein and ferritin were in high levels in
patients died than survived [27].
Will Spirulina Neutralize the Cytokine Storm?
From above results, Spirulina potentially induced
IFN and moderately induced IL-4 and IL-1 7. Spirulina
extract proved to be having anti-inflammatory effect by
inhibiting histone deacetylases (HDACs) which are
responsible for expression of inflammatory gene in
macrophages. Spirulina extract enhances global histone
H3 acetylation and degrades HDAC protein suppressing
pro-inflammatory cytokines [28]. Results demonstrated
that Spirulina extract decreased p65 binding and
H3K9/K14 acetylation at the promoters of IL-1 and tumor

Am-Euras. J. Toxicol. Sci., 12 (1): 08-13, 2020
11
necrosis factor (Tnf ) thus exerting anti-inflammatory disorders and other underlying medical conditions
effect [28].
Adverse Events: Consumption of Spirulina may be
associated with a few adverse events (AEs) related to
its nutrient ingredients and conditions of its cultivation.
In general, minor AEs associated including nausea,
insomnia, headaches etc., [29]. It may be associated with
contaminants like heavy metals, bacteria and microcystins
[27]. Spirulina may help in thinning the blood and cause
increased blood coagulation time [29]. Some studies do
not agree that spirulina affects blood coagulation time
[30, 31]. In people with food & different allergies,
spirulina consumption may be fatal [32].
After consuming 2000 mg daily for 15 days with fish
oil capsules, I have experienced bloating, feeling hot,
stomach upset and insomnia. However, lifestyle, food and
other nutrient supplements may have caused these
events. Spirulina may have some detrimental effects in a
few people. So, consult healthcare professional before
consuming it.
Avoid [29-34]: The following people should strictly avoid
spirulina consumption & suggested to consult with
healthcare professionals.
Pregnant women and children
People with autoimmune disorders
People with food & other allergies
People with liver disorders
People with phenylketonuria
People with vitamin K deficiency
To highlight, most of the vaccines under
development are focusing on different immune responses
compared to Spirulina. As Spirulina extract without
impurities was considered as safe to use color additive
mixtures in coloring foods by the US FDA (21CFR73.530)
[35]. However, Spirulina is not approved for the treatment
of any disease by the US FDA and like other dietary
supplements not regulated by the US FDA. So, there is no
guarantee that the product is accurate in dose and free of
contaminants. This review does not endorse Spirulina as
an alternate therapeutic application to any vaccine or gold
standard therapy for COVID 19 but strongly recommends
multiple randomized & controlled studies establishing its
efficacy against SARS-CoV-2 when administered as a
standalone or as a combination therapy. As Spirulina
enhances immune response, people with autoimmune
should consult healthcare professional before consuming
as dietary supplement.
Limitations: The review focused on research outcomes
including Spirulina in proliferating immune response
against various viruses. No appropriate study design
& the methodology used to impact the interpretation of
the findings. Limited data on the safety and efficacy of
spirulina in children and pregnant women. Advised to
consult healthcare professionals before consuming for
any specific indication.
Disclaimer: The author has no conflicts of interest.
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