ArticlePDF Available

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

Authors:

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
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.
REFERENCES
1. Global Economic Effects of COVID-19. Online:
https://fas.org/sgp/crs/row/R46270.pdf.
2. Mogan, K., 2020. Local climate unlikely to drive the
early COVID-19 pandemic. Online
https://www.princeton.edu/news/2020/05/18/local-
climate-unlikely-drive-early-covid-19-pandemic.
3. Paul, G.A., 2020. Coronavirus COVID-19 (SARS-CoV-
2). Online: https://www.hopkinsguides.com/hopkins/
view/Johns_Hopkins_ABX_Guide/540747/all/Coro
navirus_COVID_19__SARS_CoV_2_
4. WHO., 2020. Online: https://www.who.int/news-
room/commentaries/detail/immunity-passports-in-
the-context-of-covid-19.
5. Federal Register, 2013. Listing of Color Additives
Exempt From Certification; Spirulina Extract. Online:
https://www.federalregister.gov/documents/2013/0
8/13/2013-19550/listing-of-color-additives-exempt-
from-certification-spirulina-extract.
6. Mitch, L., 2020. T cells found in COVID-19 patients
‘bode well’ for long-term immunity. Online:
https://www.sciencemag.org/news/2020/05/t-cells-
found-covid-19-patients-bode-well-long-term-
immunity
7. UCDAVIS Study., 2020. Journal of Medicinal food;
3135-140. Online: https://www.medscape.com/
viewarticle/412276.
8. The study of Spirulina: Effects on the AIDS virus,
Cancer and the Immune System. The San Francisco
Medical research Foundation. Online:
https://lightparty.com/Health/Spirulina.html.
9. Hirahashi, T., M. Matsumoto, K. Hazeki, Y. Saeki,
M. Ui and T. Seya, 2002. Activation of the human
Am-Euras. J. Toxicol. Sci., 12 (1): 08-13, 2020
12
innate immune system by Spirulina: augmentation 19. Hayashi, T., K. Hayashi, M. Maeda and I. Kojima,
of interferon gamma production and NK cytotoxicity
by oral administration of Spirulina. International
Immunopharmacology, 2: 423-34.
10. Juszkiewicz, A., P. Basta, E. Petriczko, B. Machaliñski,
J. Trzeciak, K. uczkowska and A. Skarpañska-
Stejnborn, 2018. An attempt to induce an
immunomodulatory effect in rowers with Spirulina
extract. Journal of International Society of Sports 21. Lisheng, L., G. Baojiang, R. Jihong, Q. Guangquan
Nutrition, 15: 9.
11. Akao, Y., T. Ebihara, H. Masuda, Y. Saeki,
T. Akazawa, K. Hazeki, M. Matsumoto and T. Seya,
2009. Enhancement of antitumor natural killer cell
activation by orally administered Spirulina extract in
mice. Cancer Science, 100(8): 1494-501.
12. Nielsen, C.H., P. Balachandran, O. Christensen,
N.D. Pugh, H.Tamta, K.J. Sufka, X. Wu, A. Walsted,
M.Schjørring-Thyssen, C.Enevold and D.S. Pascoet,
2010. Enhancement of natural killer cell activity in
healthy subjects by Immulina®, a Spirulina extract
enriched for Braun-type lipoproteins. Planta Medica,
76(16): 802-8.
13. Yakoot, M. and A. Salem, 2012. Spirulina platensis
versus silymarin in the treatment of chronic hepatitis
C virus infection. A pilot randomized, comparative
clinical trial. BMC Gastroenterology, 12: 32.
14. Daoud, H.M. and E.M. Soliman, 2015. Evaluation of
Spirulina platensis extract as natural antivirus against
foot and mouth disease virus strains (A, O, SAT2).
Vet World, 8(10): 1260-1265. doi:10.14202/veterinary
world, 1260-1265.
15. David, W., 2009. Superfoods: The Food and
Medicine of the Future. North Atlantic Books.
16. Baojiang, G., 1994. Study on effect and mechanism of
polysaccharides of Spirulina platensis on body
immune functions improvement. Proceedings of
2 Asia Pacific Conference on Algal Biotechnology,
nd
Garland Publishers, pp: 24.
17. Cheng-Wu, Z., T. Chao-Tsi and Z.T.Y. Zhen, 1994.
The effects of polysaccharide and phycocyanin from
Spirulina platensis on peripheral blood and
hematopoietic system of bone marrow in mice.
Proceedings of the Second Asia-Pacific Conference
on Algal Biotechnology. National University of
Singapore, pp: 58.
18. Hayashi, O., T. Hirahashi, T. Kat h, H. Miyajima,
T. Hiran and Y. Okuwaki, 1998. Class specific
influence of dietary Spirulina platensis on antibody
production in mice. Journal of Nutritional Science
and Vitaminology, 44(6): 841-845.
1996. Calcium Spirulan, an inhibitor of enveloped
virus replication, from a blue-green alga Spirulina
platensis. Journal of Natural Products, 59(1): 83-87.
20. Hayashi, O., T. Katoh and Y. Okuwaki, 1994.
Enhancement of antibody production in mice by
dietary Spirulina platensis. J. Nutr. Sci. Vitaminol.
(Tokyo), 40(5): 431-441.
and W. Botang, 1991. Inhibitive effect and
mechanism of polysaccharide of Spirulina on
transplanted tumor cells in mice. Marine Sciences,
pp: 33-38
22. Qureshi, M., M.T. Kidd and R.A. Ali, 1996. Spirulina
extract enhances chicken macrophage functions after
in vitro exposure. Journal of Nutritional Immunology,
3(4): 35-45.
23. Qureshi, M.A., J.D. Garlich and M.T. Kidd, 1996.
Dietary Spirulina platensis enhances humoral and
cell-mediated immune functions in chickens.
Immunopharmacology and Immunotoxicology,
18: 465-476.
24. Qureshi, M.A. and R.A. Ali, 1996. Spirulina platensis
exposure enhances macrophage phagocytic
function in cats. Immunopharmacology and
Immunotoxicology, 18(3): 457-463.
25. Tornabene, T., T. Bourne, S. Raziuddin and A. Ben-
Amotz, 1985. Lipid and lipopolysaccharide
constituents of cyanobacterium Spirulina platensis
(Cyanophyceae, Nostocales) Marine Ecology
Progress Series, 22: 121-125.
26. Peter, P., 2020. Stress Enhances the Synthesis of the
Therapeutically Important Secondary Metabolites in
Cyanobacteria. World Applied Sciences Journal,
38(2): 162-170.
27. Amber, D., 2020. Cytokine storms: When the body
attacks itself. Online: https://www.bbc.com/
future/article/20200505-cytokine-storms-when-the-
body-attacks-itself.
28. Pham, T.X., Y.K. Park and J.Y. Lee, 2016.
Anti-Inflammatory Effects of Spirulina platensis
Extract via the Modulation of Histone Deacetylases.
Nutrients, 8(6): 381.
29. Blue-Green Algae. Online https://medlineplus.gov/
druginfo/natural/923.html.
30. Jensen, G.S., C. Drapeau, M. Lenninger and
K.F. Benson, 2016. Clinical Safety of a High Dose of
Phycocyanin-Enriched Aqueous Extract from
Arthrospira (Spirulina) platensis: Results from a
Am-Euras. J. Toxicol. Sci., 12 (1): 08-13, 2020
13
Randomized, Double-Blind, Placebo-Controlled 33. Schmidt, J.R., S.W. Wilhelm and G.L. Boyer, 2014.
Study with a Focus on Anticoagulant Activity and The fate of microcystins in the environment
Platelet Activation. Journal of Medicinal Food, and challenges for monitoring. Toxins (Basel),
19(7): 645-653. 6(12): 3354-3387.
31. Jensen, G.S., V.L. Attridge, J.L. Beaman, J. Guthrie, 34. Konno, T., Y. Umeda, M. Umeda, I. Kawachi,
A. Ehmann and K.F. Benson, 2015. Antioxidant and M. Oyake and N. Fujita, 2011. Rinsho Shinkeigaku;
anti-inflammatory properties of an aqueous 51(5): 330-333.
cyanophyta extract derived from Arthrospira 35. FDA, 2019. 21CFR73.530. Online:
platensis: contribution to bioactivities by the non- https://www.accessdata.fda.gov/scripts/cdrh/cfdoc
phycocyanin aqueous fraction. Journal of Medicinal s/cfcfr/CFRSearch.cfm?fr=73.530.
Food, 18(5): 535-541.
32. Le, T.M., A.C. Knulst and H. Röckmann, 2014.
Anaphylaxis to Spirulina confirmed by skin prick
test with ingredients of Spirulina tablets. Food and
Chemical Toxicology, 74: 309-310.
... The authors lament that use of such therapies remains limited in national pandemic response efforts and argue such foods warrant "urgent attention and clinical research". Pothula (2020) 65 Reviewed human and animal studies on how spirulina interacts with viruses including SARS-CoV-2. Reported it can inhibit viral replication by augmenting interferon-gamma and natural killer cell cytotoxicity, while also activating T-cells that can suppress SARS-CoV-2. ...
Article
Full-text available
The COVID-19 pandemic poses a profound threat to human health across the world. A growing body of evidence suggests that dietary choice can support pandemic response efforts. This paper asks whether spirulina, a type of edible microalgae, may offer a means of reducing COVID-19 risk. This question follows from spirulina's observed antiviral effects vis-à-vis other viral diseases. Questions about possible complementary therapies remain important due to the ongoing threat posed by COVID-19, given major gaps to vaccine rollout and the proliferation of mutant variants. The paper is based on a narrative review of the academic literature relevant to this question. The 25 papers identified were grouped and summarised, then discussed. The evidence reported suggests spirulina may have prophylactic and therapeutic efficacy against SARS-CoV-2 via several pathways, though further investigation is needed to verify the linkages identified. Incorporating spirulina into diet might thus offer a way to lower COVID-19 risk. This option may moreover be particularly helpful for at-risk populations, such as those in the Global South where many remain unvaccinated and food insecurity is widespread. This review reports findings in non-technical language and could inform actions by diverse stakeholders, including researchers, governments and households.
... Among other nutraceuticals such as glucosamine which activate the mitochondrial antiviral-signaling protein (a key mediator of type I IFN), spirulina (with the potential to enhance type I IFN in RNA virus infections) [34] or N-acetylcysteine (which promote glutathione production and protects against influenza), brewer's yeast β -glucan might prevent and control RNA viruses including coronavirus infections [35]. Indeed, not all yeast glucans act the same because of the growth conditions and this might be also a key factor in the immunomodulation process. ...
Article
The recent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), positive-sense RNA viruses, originated from Wuhan City in December 2019 and propagated widely globally. Hence, the disease caused by this virus has been declared as a global pandemic by the WHO. As of 18th February 2021, at least seven different vaccines across three platforms have been rolled out in countries and more than 200 additional vaccine candidates have been in development, of which more than 60 are at the stage of the clinical development. So far, Most of the approved vaccine manufacturers are Pfizer, AstraZeneca, and Serum Institute of India, which have been finalized by WHO. Synthetic drug-associated complications have evoked scientific attention for natural product-based drugs. There has been a surge in the antiviral compounds from natural resources along with some therapies. Cyanobacteria are the fruitful reservoir of many metabolites like sulfated polysaccharides and lectins that possess strong antiviral activities and immunity boosting effects. However, the research in this field has been relatively under-developed. The current research highlights important features of cyanobacterial antiviral biomaterials, benefits and drawbacks of cyanobacterial drugs, challenges, future perspectives as well as overview of drugs against COVID-19. In addition, we have described mutated variants and transmission rate of coronaviruses. The current research suggests that cyanobacterial species and their extracts have promising applications as potentially antiviral drug biomaterials against COVID-19. Communicated by Ramaswamy H. Sarma
Article
Full-text available
This review is an extension of my original study "Characterization of Nitrogen Stress Induced Alterations in Cyanobacterial Photosynthesis." It was clear from the literature that other secondary metabolites were produced during stress. Secondary metabolites are generally defined as compounds that are no longer needed for a primary metabolism of an organism. While most of the metabolites can be categorized as primary or secondary, there is a certain overlap. Some are essential for primary metabolism, however, are only synthesized by species and thus secondary metabolites. Under nitrogen stress conditions, the number of phycobiliproteins increased considerably, accompanied by an increase of their antioxidant activities. Moisturizers are synthesized from the secondary metabolites of extremophilic cyanobacteria. Cyanobacteria protective methods for counteracting harmful ultraviolet radiation from the sun are now widely discussed. Several clinical studies have found a high efficacy secondary metabolite in cancer treatment. Low external pH triggers heat shock proteins which have medicinal principles including antimicrobial and antioxidative action. In HIV patients, insulin sensitivity increases more when Spirulina is used as a nutritional supplement instead of soya. Cyanobacteria provide a rich wealth of chemicals for the discovery of lead compounds and new medicines that are safe yet promising. Pharmaceutical companies should conduct clinical trials on several bioactive molecules obtained from cyanobacteria exhibiting a broad spectrum of activities, such as antitumor, antibacterial and antiviral effects and protease inhibition. Recently, also a growing interest has been shown in the development of bioactive compounds for trade or medical applications.
Article
Full-text available
By the end of 2019 the first cases of severe pneumonia of unknown origin were reported in Wuhan, China. The causative agent was identified as a novel b-coronavirus SARS-CoV-2 and the disease was named COVID-19. Since the beginning of 2020, the infection has spread worldwide, which led the WHO to declare COVID-19 a public health emergency of international concern and to characterize the current situation as a pandemic. The transmission occurs mainly via respiratory droplets and the incubation period ranges from 2 to 14 days. Most cases are mild, but some patients develop severe pneumonia with acute respiratory distress, septic shock and multi-organ failure. The most common symptoms include fever, dry cough, myalgia and shortness of breath. Characteristic laboratory findings are normal white blood cell count or mild leukopenia, marked lymphopenia, in severe cases elevated CRP, procalcitonin, LDH, and D-dimer are commonly found. Typical imaging findings include multifocal peripherally distributed ground-glass opacities or consolidations, interlobular septal thickening, crazy paving appearance and cystic changes. The overall case fatality rate is estimated to range from 1 to 3 %, however, it is dependent on age and underlying medical comorbidities. Current potential treatment options include hydroxychloroquine, remdesivir, lopinavir/ritonavir and convalescent plasma.
Article
Full-text available
The goal for this study was to evaluate safety regarding anticoagulant activity and platelet activation during daily consumption of an aqueous cyanophyta extract (ACE), containing a high dose of phycocyanin. Using a randomized, double-blind, placebo-controlled study design, 24 men and women were enrolled after informed consent, and consumed either ACE (2.3 g/day) or placebo daily for 2 weeks. The ACE dose was equivalent to ∼1 g phycocyanin per day, chosen based on the highest dose Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. Consuming ACE did not alter markers for platelet activation (P-selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen; the difference in AST levels between the two groups was significant at 2 weeks (P < .02). Reduced levels of alanine transaminase (ALT) were also seen in the group consuming ACE (P < .08). Previous studies showed reduction of chronic pain when consuming 1 g ACE per day. The higher dose of 2.3 g/day in this study was associated with significant reduction of chronic pain at rest and when physically active (P < .05). Consumption of ACE showed safety regarding markers pertaining to anticoagulant activity and platelet activation status, in conjunction with rapid and robust relief of chronic pain. Reduction in AST and ALT suggested improvement in liver function and metabolism.
Article
Full-text available
We previously demonstrated that the organic extract of Spirulina platensis (SPE), an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs) play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β), but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα) promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect.
Article
Full-text available
Aim: This work was aimed to document the antiviral activates of Spirulina platensis extract against foot and mouth disease virus (FMDV) different types to evaluate its replication in Baby Hamster Kidney (BHK) cell culture and in baby mice. Materials and methods: Cytotoxicity assay studied for S. platensis extract on BHK cells to determine the non-toxic dose. The non-toxic dose of Spirulina extract was mixed with each type of FMDV (A, O, SAT2). Then 10-fold dilutions from each mixture were done. FMDV titer for each type of treated FMDV was calculated to evaluate the antiviral activity of the Spirulina extract against FMDV. Furthermore, old baby Swiss mice were inoculated with 0.1 ml intraperitonially from the mixture of FMDV different types and different concentration of Spirulina extracts. After 48 h post inoculation, all the baby mice examined to evaluate the antiviral action of Spirulina extract. Results: The result showed that the non-toxic doses of S. platensis (50 ug/ml) revealed 35.7%, 28.5%, and 31% reductions in FMDV titers Type O, A, and SAT2 on BHK cells, respectively. The same non-toxic dose gave 50% of the inhibitory concentration in baby mice without cytotoxic effect. Conclusion: This study confirmed the biological activity of the ethanol extract of S. platensis against FMDV Types O, A, and SAT2. From the results, S. platensis could be useful as antiviral lead to limitation of infection among animals during outbreaks but further studies need to evaluate the S. platensis on experimental or natural infected farm animals to establish the effective dose side affected period of treatment of S. platensis.
Article
Immulina®, a commercial extract of Spirulina (Arthrospira) platensis, is a potent activator of THP-1 monocytes and CD4+ T cells in vitro and enhances several immunological functions in mice. In this study we further characterize Immulina® by determining that Braun type lipoproteins that are responsible for a major portion of the in vitro monocyte activation exhibited by this material. In order to understand the effect of Immulina® on the activity of NK cells, a pilot study was conducted on ten healthy North American individuals who supplemented their diet with Immulina® (400mg/day) for seven days. We observed a 40% average increase in the killing of K-562 tumor cells by NK cells (p=0.01) after Immulina® supplementation. A similar increase in tumor cell killing by NK cells was observed in a separate placebo-controlled, cross-over study involving11 healthy Danish subjects, who displayed increases by 83% (p=ns) and 54% (p=0.03), after ingestion of Immulina® (200mg/day and 400mg/day, respectively) for seven days, as assessed using a mononuclear cell: K-562 ratio of 5:1. The increased cytolytic activity was apparently not associated with an increased activity per cell, since the expression of CD69 by NK cells remained unchanged. Rather, it could be explained by an increase in peripheral NK cell numbers by 49% (p=0.08) and 40% (p=0.03), following ingestion of Immulina® (200mg/day and 400mg/day, respectively). NKT or T cell numbers did not change. We found no effect of Immulina® on the ratio between CD56bright and CD56dim NK cells. In summary, two independent studies showed enhancement of NK-cell cytotoxicity following administration of Immulina® 400mg/day for seven days.
Article
Spirulina (Arthrospira platensis), blue-green microalgae, has high content in proteins, γ-linoleic acid and vitamins and therefore gained popularity as food supplement. According to the Food and Agriculture Organization of the United Nations Spirulina is also an interesting alternative and sustainable protein source with the growing world population. We present a case of a 17-year-old male, who developed anaphylaxis the first time he ingested a Spirulina tablet. Skin prick test with diluted Spirulina tablet was positive. Further skin prick testing with separated ingredients (Spirulina platensis algae, silicon dioxide, inulin and magnesium stearate) was only positive for Spirulina platensis algae and negative in controls, confirming the allergy was caused by Spirulina and not by one of the additives. This case report shows that diagnosis of Spirulina allergy can safely be made by skin prick test with dilutions of the A. platensis or even more simple by skin prick test with the diluted tablet. Since Spirulina has gained popularity as food and nutritional supplement, it is important to realize the potential risk of this dietary supplement. Before Spirulina is produced and consumed on a wider scale, allergenicity risk assessment should be performed, including investigation of potential crossreactivity with well-known inhalant allergens and foods.
Article
The effects of Spirulina platensis (Sp) extract exposure on chicken macrophages were examined. Sephadex-elicited abdominal exudate macrophage monolayers were exposed to varying concentrations (10 to 40 μg/ml) of Sp for 1 to 16 hours. Spirulina-treated macrophages exhibited phenotypic changes in terms of increased spreading and vacuolization with minimal cytotoxicity. Percentage of phagocytic macrophages for unopsonized sheep red blood cells (SRBC) and average number of internalized SRBC was significantly higher in Sp-treated macrophages as compared to the sham-treated controls. However, phagocytosis of opsonized SRBC was not affected by Sp-treatment. Macrophage cultures exposed to Sp produced a factor in their culture supernatant with tumoricidal potential which was similar in reactivity to the one produced by macrophages after exposure to lipopolysaccharide. The ability of splenic natural killer cells to kill tumor cell targets was not affected by Sp treatment. These findings suggest that Spirulina exposure enhances selected effector functions of cells of the chicken immune system after in vitro exposure.