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Antiviral activity of Spirulina maxima against Herpes simplex virus type 2
Abstract
Spirulina has been used in a variety of practical applications in biotechnology and medical sciences. This paper presents the antiviral activity found in a hot water extract (HWE) of a commercial preparation of Spirulina maxima, studied by a microplate inhibition assay, using several viruses. The HWE inhibited the infection for: herpes simplex virus type 2 (HSV-2), pseudorabies virus (PRV), human cytomegalovirus (HCMV), and HSV-1, and the 50% effective inhibition doses (ED(50)) were 0.069, 0.103, 0.142, and 0.333 mg/ml for each virus, respectively. For adenovirus the inhibition was less than 20%, and no inhibition was found for measles virus, subacute sclerosing panencephalitis virus (SSPE), vesicular stomatitis virus (VSV), poliovirus 1 and rotavirus SA-11, at concentrations of 2 mg/ml of the HWE. The highest antiviral activity was for HSV-2, with a selectivity index of 128. The antiviral activity was not due to a virucidal effect. Herpesvirus infection was inhibited at the initial events (adsorption and penetration) of the viral cycle. To initiate the isolation and identification of the compound that exhibits the antiviral activity of S. maxima, some extracts made by using several solvents with different polarity were evaluated by microplate inhibition assay using HSV-2. The highest antiviral activity was detected in the methanol-water 3:1, which suggests that the antiviral activity is probably due to highly polar compounds.
... In 1998, Ayehunie et al. demonstrated that aqueous extract from S. platensis inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells (LC) 26 . Later polysaccharide fractions of S. platensis were analyzed, showing strong antiviral activity against CMV, HSV-1, HSV-2, HSV-6, Pseudorabies virus (PRV), and human immunodeficiency virus type 1 (HIV-1) 27,28 . Jang and Park found that a compound isolated from A. maxima, inhibited HIV-1 infection in the human T cell line MT4 29 . ...
... In our experiments we used a 0.003 MOI (100 TCID 50/ml ) that produced a plateau at 72 hpi, assessed by RT-PCR. Other research groups have used similar viral loads as we used for our experiments to measure antiviral activity 28,33,36 . It would be interesting to performed further experiments using higher viral loads to understand if the algae tested herein, could have the antiviral activity in early stages of infection. ...
... According to Indrayanto et al. 43 , the ideal treatment should have a SI above 10. This finding is similar to the one reported by Hernandez et al. 28 for A. maxima against Herpes Simplex Virus type 1 and 2 (HSV-1 and HSV-2) whose SI were 26 and 128 respectively. Magdalena et al. 44 reported for C. vulgaris and A. maxima against Mayaro virus (MAYV) SI of 51.16 and 25.5 respectively 28,45 . ...
Chlorella spp., Spirulina spp., and fucoidan dry powders, are commercialized as food supplements
and are considered safe for human consumption. Their broad‐spectrum antiviral properties have
been studied, however, their effect against SARS‐CoV‐2 remains unknown. We investigated the potential antiviral activity of three algae powders: Chlorella vulgaris, Arthrospira maxima (Spirulina) and fucoidan purified from marine brown algae Sargassum spp. against SARS‐CoV‐2 infection in vitro. Vero cells were incubated with 70 μg/ml of each algae powder and either 50 or 100 TCID50/ml of SARS‐ CoV‐2, in two types of experiments (pretreatment and simultaneous) and comparing two kinds of solvents (DMEM and DMSO). Chlorella vulgaris powder, inhibited SARS‐CoV‐2 infection in all assays; viral RNA was significantly reduced in supernatants at 24, 48, 72, and 96 h post‐infection, the highest difference in viral load (8000‐fold) was observed after 96 h. Arthrospira maxima powder inhibited SARS‐CoV‐2 infection using 50 TCID50/ml for both experimental schemes, but protection percent was lower when viral inoculum was increase to 100 TCID50/ml; viral RNA decreased 48 h after infection, reaching a 250‐fold difference at 72 h. Fucoidan powder partially inhibited SARS‐CoV‐2 infection since no CPE was observed in 62.5% of trated cultures in DMEM, but the antiviral activity was increased
to 100% of protection when DMSO was used as solvent. All the algae samples showed high antiviral activity against SARS‐CoV‐2 with a SI above of 18. These results suggest that all three algae samples are potential therapeutic candidates for the treatment of COVID‐19.
... In such a case, higher infectious titers would be measured than induced by a fresh extract. Therefore, based on previous studies 32, 55,58 and since we assumed that 1 h is sufficient for the virus to enter the cells, further experiments were carried out without constant virus exposure. Thus, to remove unabsorbed viruses after the infection phase the infectious supernatant of all samples and also the supernatant of the replication controls was discarded after inoculation. ...
... Since the SI of antiviral extracts and substances depends not only on the species, extraction method and the degree of purification, but also on the virus and the host cells used, cross-study comparisons must be done with caution and are better suited for comparing orders of magnitudes than concrete values. In a similar study performed with hot water extracts from A. platensis, the replication of HSV-1 and HSV-2 was inhibited by 50% at a concentration of 0.3 mg mL −1 showing IC 50 values in the same order of magnitude and an SI of 26 49,58 . However, when using purified products such as sulphated polysaccharides and SQDG, significantly lower IC 50 values were achieved where replication of HSV and HCMV was inhibited by 50% at concentrations in the range of μg mL −121,27 . ...
... For the investigation of antiviral properties of the microalgal extracts, CCB cells were seeded in 96-well plates (60 000 cells cm −2 ) and incubated at 25 °C for 24 h prior to the treatment. As in comparable studies extracts were tested in five to six different concentrations, obtained by consecutive dilutions (1:2) with DMEM as described above and mixed with virus stock to reach the appointed MOI 32,34,58 . The concentration of the extracts was determined by taking the dry extract weight, the solvent volume and the dilution level into account and expressed in mg of dried extract per mL (mg de mL −1 ). ...
Microalgae are possible sources of antiviral substances, e.g. against cyprinid herpesvirus 3 (CyHV-3). Although this virus leads to high mortalities in aquacultures, there is no treatment available yet. Hence, ethanolic extracts produced with accelerated solvent extraction from six microalgal species ( Arthrospira platensis , Chlamydomonas reinhardtii , Chlorella kessleri , Haematococcus pluvialis , Nostoc punctiforme and Scenedesmus obliquus ) were examined in this study. An inhibition of the in vitro replication of CyHV-3 could be confirmed for all six species, with the greatest effect for the C. reinhardtii and H. pluvialis crude extracts. At still non-cytotoxic concentrations, viral DNA replication was reduced by over 3 orders of magnitude each compared to the untreated replication controls, while the virus titers were even below the limit of detection (reduction of 4 orders of magnitude). When pre-incubating both cells and virus with C. reinhardtii and H. pluvialis extracts before inoculation, the reduction of viral DNA was even stronger (> 4 orders of magnitude) and no infectious viral particles were detected. Thus, the results of this study indicate that microalgae and cyanobacteria are a promising source of natural bioactive substances against CyHV-3. However, further studies regarding the isolation and identification of the active components of the extracts are needed.
... Recently, many bioactive polysaccharides and oligosaccharides originating from microalgae have also been discovered with different bioactivities (FIG. 3) [25,35,39,[68][69][70][71][72]. ...
... The antiviral activity is one of the most studied bioactivities demonstrated by microalgaederived sulfated polysaccharides. Several studies have reported that the polysaccharides are secreted into the medium by specific microalgal species such as Spirulina maxima, Arthrospira platensis, Margalefidinium polykrikoides exhibit antiviral activities [70,72,73]. To date, polysaccharides from the red alga Porphyridium and the cyanobacterium Arthrospira are well-known anionic sulfonated polymers, demonstrating broad-spectrum antiviral activity against different viruses, including Varicella zoster and Herpes simplex, measles, mumps, and human cytomegalovirus. ...
... To date, polysaccharides from the red alga Porphyridium and the cyanobacterium Arthrospira are well-known anionic sulfonated polymers, demonstrating broad-spectrum antiviral activity against different viruses, including Varicella zoster and Herpes simplex, measles, mumps, and human cytomegalovirus. Some studies showed the potency of polysaccharides to inhibit the human immunodeficiency viruses (HIV) [70,71]. Although it has been proposed that polysaccharides could inhibit virus infection by preventing viral particles from penetrating into hosts, or inhibiting attachment/adsorption, or restrain virus replication during its early phases, mechanisms for antiviral activity have not been fully revealed [36]. ...
Microalgae are a major primary producer in the ocean, contributing up to 50% of global primary production. Bioactive compounds from microalgae include carotenoids, such as beta-carotene, lutein, and essential fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, have been attractive as natural products for decades. Recently, polysaccharides and their derivatives from marine microalgae have drawn much attention as the biodiversity of microalgae offers great opportunities for discovering novel bioactive compounds. Marine microalgae, including diatoms, are rich sources of sulfated polysaccharides, which have shown antiviral, antioxidant, antiinflammatory, antiparasitic, and antitumor activities. Although the mechanisms underlying the biological activities of microalgal polysaccharides are not fully understood, their positive effects on the human body are mostly associated with their prebiotic activity. In this review, a variety of microalgae with different types of polysaccharides and oligosaccharides are described. For the screening of bioactive compounds, extraction and purification methods are also introduced to explore the composition and efficacy of polysaccharides in microalgae. Biosynthetic pathways of polysaccharides are summarized, and their biotechnology applications are illustrated accordingly. This chapter demonstrates the biological activities of polysaccharides and their derivatives from microalgae and potential use in human health and other industrial applications. The current challenges in the microalgal polysaccharide field are highlighted. Finally, conclusions and future scope are also provided.
... Interestingly, current evidence suggests that the early steps of infection (attachment, fusion, and penetration) are particularly affected. More specific examples include the inhibition of influenza-mediated hemagglutination (Chen et al., 2016), reduced infection of cells (Joseph et al., 2020) by corona-based pseudotype viruses (CoVpvs) after preincubation with Spirulina extracts, and inhibition of the herpes simplex virus HSV-2 if administered on the first two hours after infection (Hernández-Corona et al., 2002). In contrast, the effect of Spirulina on the human immunodeficiency virus (HIV) might have a different mechanism occurring after the penetration of the cell by the viral particles (Jang and Park, 2016). ...
... The effect of Spirulina hot water extract (HWE) on several viruses, including HSV-1 and HSV-2, was evaluated using the TCID50 assay in Vero cells (Hernández-Corona et al., 2002). HWE was added to cells infected with the virus at different time points after infection. ...
... HWE was added to cells infected with the virus at different time points after infection. HWE inhibited HSV-2 when applied on the first two hours following infection, suggesting the HWE effects the first steps of the viral cycle (adsorption and penetration) (Hernández-Corona et al., 2002). Chirasuwan et al. (2009) showed that certain Spirulina (ethyl acetate extract) fractions Complimentary Contributor Copy had high activity against HSV-1. ...
Microalgae usually called “Spirulina” in the literature and in commercial packages have been studied as potential sources of protein for food and feed supplementation. These microalgae are produced industrially worldwide, being recognized as GRAS (Generally Recognized as Safe) by the Food and Drug Administration (USA) and accepted by the European Union for human consumption. Apart from a high protein content and balanced amino acid composition, its biomass contains compounds with antioxidant, anti-inflammatory, anti-tumor, anti-viral and anti-microbial activities. Some of these compounds have been determined to boost the immune system and prevent diseases such as hyperglycemia, cancer, diabetes, hypertension, cardiovascular and respiratory disorders. It has also been suggested that the supplementation with Spirulina biomass and/or its extracts could help immune systems to fight different viral infections, including those by SARS-CoV2, the etiologic agent of COVID-19. This immunity boosting activity has been related to the presence of some polysaccharides, carotenoids, phycobiliproteins, fatty acids and biopeptides in the biomass. In this context, this chapter will address the boosting effect of the immune system by Spirulina exploring its antiviral activity and respective mechanisms. The applications of the biomass as a supplement and nutraceuticals production will be also address.
... Interestingly, current evidence suggests that the early steps of infection (attachment, fusion, and penetration) are particularly affected. More specific examples include the inhibition of influenza-mediated hemagglutination (Chen et al., 2016), reduced infection of cells (Joseph et al., 2020) by corona-based pseudotype viruses (CoVpvs) after preincubation with Spirulina extracts, and inhibition of the herpes simplex virus HSV-2 if administered on the first two hours after infection (Hernández-Corona et al., 2002). In contrast, the effect of Spirulina on the human immunodeficiency virus (HIV) might have a different mechanism occurring after the penetration of the cell by the viral particles (Jang and Park, 2016). ...
... The effect of Spirulina hot water extract (HWE) on several viruses, including HSV-1 and HSV-2, was evaluated using the TCID50 assay in Vero cells (Hernández-Corona et al., 2002). HWE was added to cells infected with the virus at different time points after infection. ...
... HWE was added to cells infected with the virus at different time points after infection. HWE inhibited HSV-2 when applied on the first two hours following infection, suggesting the HWE effects the first steps of the viral cycle (adsorption and penetration) (Hernández-Corona et al., 2002). Chirasuwan et al. (2009) showed that certain Spirulina (ethyl acetate extract) fractions Complimentary Contributor Copy had high activity against HSV-1. ...
... Spirulina naturally can inhibit the activity of viruses as it has all the biomolecules which can build a strong immune system that can scavenge free radicals (Ali & Saleh, 2012). The extracts isolated from S. platensis and S. maxima were reported to possess antiviral properties (Hernandez-corona et al., 2002;El-Baz et al., 2013;Kameshwari et al., 2020). The antiviral activity of Spirulina mostly depends on the richness of proteins (phycocyanin), sulphated polysaccharide fragments, fatty acids (sulpholipids), minerals, and some other constituents (Nuhu, 2013;Kameshwari et al., 2020). ...
... The treatment of allophycocyanin to the host cells before viral infection showed higher antiviral activity than treatment after infection (Shih et al., 2003). Other than S. platensis, Hernandez-corona et al., (2002) reported that methanol-water (3:1) extract of S. maxima exhibited the highest antiviral activity on HSV-2 among hexane, chloroform, methanol, and hot water extracts. S. maxima extract prepared using hot water showed less than 20% inhibition on adenovirus type 3 with IC50 5.2 mg/mL and no inhibition was observed at concentrations below 2 mg/mL (Hernandez-corona et al., 2002;Rahman et al., 2006). ...
... Other than S. platensis, Hernandez-corona et al., (2002) reported that methanol-water (3:1) extract of S. maxima exhibited the highest antiviral activity on HSV-2 among hexane, chloroform, methanol, and hot water extracts. S. maxima extract prepared using hot water showed less than 20% inhibition on adenovirus type 3 with IC50 5.2 mg/mL and no inhibition was observed at concentrations below 2 mg/mL (Hernandez-corona et al., 2002;Rahman et al., 2006). (2020), reported that L-asparaginase (L-AsnA) purified from S. maxima showed a dose-dependent antiviral effect on Coxsackie B3 (CSB3) virus where 17.03 μg/mL of L-AsnA inhibited 50% of CSB3 virus and suggested that inhibition of viral replication cycle might be the mechanism behind the antiviral effect. ...
Viruses can spread worldwide and the early detection of emerging infectious diseases and outbreaks in humans and animals is important for effective surveillance and prevention. Viruses such as human immunodeficiency virus (HIV), swine flu, and influenza virus are some of the viruses that spread diseases worldwide. However, the non-availability of effective antiviral drugs and the drug-resistance among the virus and host have become the major problems in controlling viral infections. The natural products from microalgae can be an alternative therapeutic agent to control viral infections in humans. Spirulina is a well-known cyanobacterium that has been consumed by humans as a food supplement for more than centuries without side-effects. Spirulina possesses high nutritional values and provides numerous health benefits to the consumers. Spirulina can be an alternative natural therapeutic agent for numerous virus infections as it contains several bioactive compounds with proven antiviral effect on enveloped viruses (Herpes simplex virus, measles virus, mumps virus) and non-enveloped viruses (astrovirus, rotavirus) by preventing the spread of the virus in the host cells. Spirulina also serves as a natural supplement that strengthens the immune system. This review focuses on the antiviral properties and immunostimulant effects of Spirulina as a potential therapeutic supplement on human health.
... In accordance with the preceding report, the polysaccharides of Spirulina maxima were subjected to hot water extract treatment to determine the antiviral activity against HSV-2 and HSV-1 infections; where the concentrations of 69 and 333 μg/ml have revealed moderate IC50 values on it. According to Hernandez-Corona et al. 61 the hot water extraction of s. maxima has revealed effective inhibitory potential in the tested viruses, including HSV-2 infection, pseudorabies virus (PRV), HCMV, and HSV-1; whereas, it was registered that the 50% effective inhibitory doses (ED50) for each virus were found to be 0.069, 0.103, 0.142, and 0.333 µg/ml, respectively. Worldwide, the Influenza viruses are circulating as seasonal epidemics which mainly affect respiratory tracts. ...
... It prevents viral entry into host cells and the development of syncytium even while administered at lower doses. 61 It has also been shown to have antiviral activity against enveloped viruses, most notably to influenza A virus (IAV). 29,54 Similarly, the cyanobacterium Aphanothece halophytica consisted of a large amount of sulfated exopolysaccharide, which is made up of arabinose, rhamnose, fucose, mannose, glucose, galactose, glucuronic, and sulfuric acids. ...
Most of the medical and nonmedical research labs, all around the world, are racing against time to produce an effective vaccine or an antiviral medicine for coronavirus disease 2019 (COVID‐19). Conventional medicines and novel nano‐materials including chemical and herbal‐based compounds are all into positive trials toward coronaviruses and other pandemic infections. Among them, natural immune boosters have attracted physicians because of their longevity and reliability for fewer side effects. This is a review article with a detailed picture of an unexplored antiviral source with maximum potency in curing viral infections. Cyanobacteriae have been known for centuries and are rich in secondary metabolites of proteins, biopeptides, and polysaccharides for prominent antiviral action against chest infections. But detailed exploratory research is required to purify, scale‐up, and commercialize the pharmacologically active agents from these drug reserves.
... Consumption of a supplement containing Spirulina extract leads to an increase in Thelper lymphocytes in HIV-infected patients, and a reduction in viral load has also been found [105][106][107][108]. There have been other reports of the antiviral activity of spirulina against viruses such as cytomegalovirus, human immunodeficiency virus-1 (HIV-1), influenza A virus, Herpes simplex mumps virus, and measles [109][110]. Water-based spirulina extract inhibits the penetration and replication of herpes simplex virus-1 (HSV-1) cells [111]. ...
Algae, as well as Arthrospira platensis, have a wide range of biologically active constituents that determine different pharmacological properties. They are also the basis for developing various new nutritional compositions and supplements. This review summarizes the application of algae and Arthrospira platensis in pharmaceutical technology and food over the last 20 years with an emphasis on the beneficial effects of spirulina on human health, considering its nutritional value and therapeutic properties. A detailed literature review was conducted in scientific databases for over 20 years, such as PubMed, ScienceDirect, ResearchGate, and Google Scholar. Relevant information is summarized and interpreted. The permanent research process leads to the development of new preparations to inhibit the growth of cancer cells, reduce the aging of cells, increase the immune system's efficiency, protect against infectious diseases, etc. In vivo studies show specific mechanisms of neuroprotection, appetite regulation, and prevention of neurodegenerative and psycho-cognitive pathologies. Algae and Arthrospira platensis, with their biologically active metabolites, are essential raw materials for producing various pharmaceutical products and functional foods with high nutrient content. Their use depends on the preservation of their biodiversity. In connection with their biosafety and the understanding of the biological effects on the human organism, it is necessary to continue their study.
... It has antiviral properties against influenza A, human cytomegalovirus, Herpes simplex virus (HSV) 1 and 2. In addition, it prevents virus infection from starting, including the binding and internalization steps (Kanekiyo et al. 2007). Calcium spirulan (Ca-SP)-It is a sulfated polysaccharide obtained from Spirulina platensis hot water extract that has antiviral efficacy against HSV, measles, mumps, human immunodeficiency viruses (HIV), influenza A, and Henoch-Schonlein Purpura (HSP) (Hernández-Corona et al. 2002). It inhibits the virus from entering the host cell and lowers melanoma lung metastasis by preventing tumor cells from invading the basal membrane (Khandia et al. 2019). ...
Cyanobacteria are photosynthetic prokaryotes that have a variety of biological activities and can be used as dietary supplements. Because of its high nutritional, protein, and digestibility content, it is utilized as a meal supplement. Spirulina sp., Anabaena sp., Microcystis sp., Nostoc sp., Lyngbya sp., Oscillatoria sp., and other cyanobacteria create a wide range of secondary bioactive
metabolites with diverse biological functions. Cyanobacteria produce various physiologically active and chemically diverse compounds such as saccharides, fatty acid amides, lipopeptides, cyclic and acyclic peptides, and alkaloids. More than half of marine cyanobacteria could be used to extract bioactive compounds that can destroy cancer cells by causing apoptosis. Their effectiveness as an antiviral, antitumor, antibacterial, anti-HIV, and dietary additive is extensively documented. However, such drugs are in various phases of clinical studies, and only a few have made it to the market. This chapter examines the bioactive chemicals in cyanobacteria with antiprotozoal, antibacterial, anti-inflammatory, anticancer, antioxidant, and antiviral properties.
... S. platensis and Spirulina maxima express antiviral properties against human diseases such as HSV-1 and HSV-2. 15,16 Hepatitis is a serious threat, 17,18 and the need for drugs against this is a need of the hour. Some researchers have identified potential compounds with antihepatitis activity. ...
Microalgae are photosynthetic cell factories that produce a spectrum of bioactive compounds extensively used for various applications. Owing to the increase in antibiotic resistance among microbial pathogens, there is a significant thrust for identifying new treatment strategies, and antimicrobial peptides (AMPs) generation is one such method. These AMPs have multiple roles and are active against bacteria, fungi, and viruses. Such peptides synthesized in microalgae have a significant role in medical application, managing aquaculture-associated diseases, and the food industry. To increase their effectiveness and novel peptides, genetically modified microalgae are used as cell factories. With the advancement of new technologies like the CRISPR-Cas system, new avenues are opened for developing novel AMPs using microalgae. This review gives us insight into the various AMPs produced by microalgae and multiple technologies involved in creating such therapeutically essential molecules.
... The most likely antiviral components of spirulina are the protein phycocyanin, sulfated polysaccharide fragments, GLA and some sulpholipids (Anvar and Nowruzi 2021). Sulfated polysaccharide of Spirulina ejects its antiviral activity by suppressing the replication of human cytomegalovirus (HCMV), herpes simplex, (HSV-1, HSV-2) (Hernández-Corona et al. 2002) human immunodeficiency (HIV-1) (Ngo-Matip et al. 2015), influenza A, mumps, measles and white spot syndrome viruses (Anvar and Nowruzi 2021). Allophycocyanin extracted from Spirulina platensis, has revealed an antiviral act against enterovirus 71 (Abd El-Baky and El-Baroty 2020). ...
Nutraceuticals have for several years aroused the interest of researchers for their countless properties, including the management of viral infections. In the context of the COVID-19 pandemic, studies and research on the antiviral properties of nutraceuticals have greatly increased. More specifically, over the past two years, researchers have focused on analyzing the possible role of nutraceuticals in reducing the risk of SARS-CoV-2 infection or mitigating the symptoms of COVID-19. Among nutraceuticals, turmeric, extracted from the rhizome of the Curcuma Longa plant, and spirulina, commercial name of the cyanobacterium Arthrospira platensis, have assumed considerable importance in recent years. The purpose of this review is to collect, through a search of the most recent articles on Pubmed, the scientific evidence on the role of these two compounds in the fight against COVID-19. In the last two years many hypotheses, some confirmed by clinical and experimental studies, have been made on the possible use of turmeric against COVID-19, while on spirulina and its possible role against SARS-CoV-2 infection information is much less. The demonstrated antiviral properties of spirulina and the fact that these cyanobacteria may modulate or modify some mechanisms also involved in the onset of COVID-19, lead us to think that it may have the same importance as curcumin in fighting this disease and to speculate on the possible combined use of these two substances to obtain a synergistic effect.
... Moreover, an acidic polysaccharide nostoflan was reported to have antiviral activity against HSV-1, HSV-2, human cytomegalovirus, and influenza A virus [81]. Polysaccharides from Spirulina maxima and S. platensis have also shown antiviral potential against different viruses [82]. These findings suggest that cyanobacterial polysaccharides are having good potential to be used as starting material for antiviral drug development. ...
... El incremento de la concentración de exopolisacáridos disueltos y la disminución de los carbohidratos de biomasa en este segundo ensayo con PCC 7936 (cepa capsulada), en condiciones no diazotróficas, se explicaría como la permanente solubilización de la capsula debido a las condiciones del cultivo. Algunas investigaciones soportan esta hipótesis, de hecho al menos para Anabaena flos-aquae (Moore y Tischer, 1964; Phormidium (Gloaguen et al. 1995), Anabaena C5 (Gantar et al. 1995), Cyanospira capsulata (Vincenzini et al. 1990), y Aphanothece halophytica GR02 (Li et al. 2001b Hernández-Corona et al. 2002), y del alga roja Porphyridium cruentum (Fábregas et al. 1998). En biomedicina estos polímeros son analizados como agentes hemostáticos para la reparación de heridas, por las propiedades antiinflamatorias contra edemas de la piel, o para el tratamiento de la dermatitis atópica (Bhatnagar et al. 2014a;Garbacki et al. 2000;Fukushima et al. 2016). ...
The cyanobacteria is a photosynthetic microorganism group that show up on earth around 2,4 billion years. They are prokaryotic organisms located by its characteristics in the group of Gram-negative bacteria. The cyanobacteria show complex metabolic ways for the carbohydrates synthesis; that allowed them to synthetize intracellular carbohydrates, polymer reserves like glucan and extracellular polysaccharides structurally complex. The extracellular polysaccharides are presented associated with the cellular surface form of envelops, capsules and viscous material and the polysaccharides released into the environment. The dissolved exopolysaccharides are soluble portions of polysaccharide material released into the environment throughout the external envelops or byproduct by complex biosynthetic processes. The importance of this polymers lies in the ease of recovery of the culture medium and due to their complex structure includes sulfate, phosphate, acetate groups, uronic acids, protein fractions and also a complex structure and monosaccharide composition, which gives them interesting physicochemical properties for various fields such as: biomedicine, pharmaceutics, food industry, remediation of residual effluents, etc. The use of cyanobacteria in wastewater treatment has been widely documented in the pig slurry purification with interesting results shown. However, is indispensable, to evaluate the remediation potential of these microorganisms in other types of industrial effluents.
... This polymer has proven effective against enveloped viruses, including HSV-1, MV, HCMV, IAV, and HIV-1. This SPS dosedependently inhibited HSV1 entry and replication [47,80] and did not suppress host cell function [81]. In this case, Ca-Sp is targeted not only at the stage of adsorption and penetration of viruses into cells but also at some stages of replication. ...
Microalgae (MA) and cyanobacteria (CB) are currently attracting much attention from scientists due to the high biological activity of many secondary metabolites of these aquatic organisms. This review presents up-to-date modern data on the prospects for using polysaccharides (PS) of these marine aquatic organisms as effective and practically safe antiviral agents. These natural biopolymers are polyvalent compounds, which allows them to bind to several complementary biological target receptors. Particular emphasis is placed on the exopolysaccharides (EPS) Spirulina sp. (Arthrospira sp.), Porphyridium sp., Chlorella sp., and Euglena sp., whose antiviral activity makes them promising for the creation of drugs, biologically active food supplements, and products for functional nutrition. The mechanisms of the biological action of PS and the targets of these compounds are presented with a brief description of PS's anti-inflammatory, immunomodulatory and antioxidant actions, which make the most significant contribution to the antiviral effects. The authors hope to draw the attention of researchers to the use of water extracts and polysaccharides of microalgae and cyanobacteria as potential broad-spectrum antiviral agents that can become the basis for new antivirus strategies.
... Cyanobacterial extracts with lipophilic nature are more eminent as compared to hydrophilic extracts (Patterson et al. 1994). Reports of Hernández-Corona et al. (2002) showed that hot water extract from Spirulina maxima can antagonistically act on Herpes simplex virus type 2 (HSV-2). Acidic polysaccharides, like calcium spirulan (Ca-SP) is a potent inhibitor of herpes simplex virus-1 which is commonly released by cyanobacterium Arthrospira platensis. ...
Ecological studies have helped to understand the diverse nature of cyanobacteria and to uncover its long history due to morphological plasticity and ecological flexibility. Cyanobacteria are found flourishing all over different habitats on earth, including the extreme environments. They are major players in the biogeochemical cycling of carbon, nitrogen, and oxygen. Cyanobacteria are oxygenic autotrophs and are major nitrogen fixers. The inherent ability to fix atmospheric nitrogen makes them extremely important in maintaining the stability and equilibrium of the ecosystem, thereby providing them a better competitive advantage in environments where nitrogen concentration is comparatively low. The adaptations to different kinds of environmental conditions including extreme pH, salinity, and temperature, make them the most diverse group of organisms on the earth. This feature of adaptability has helped to cultivate cyanobacteria successfully in laboratory conditions as well. Not only ecologically, but cyanobacteria are morphologically diverse too and this morphological complexity makes the taxonomy of this group very difficult and confusing. This complicacy impedes the accurate identification and classification of cyanobacteria, thus making it interesting but challenging. The taxonomic identity is complicated because of confusions due to morphological plasticity and the role of ecology in classification, thus leading to
erroneous identifications. The gradual shift from classical morphological taxonomy to molecular taxonomy has led to the development of a combined “polyphasic approach” which has resulted into the amalgamation of morphological, ecological, genetic, molecular and phylogenetic traits. Thus, cyanobacterial taxonomy has been substantially enhanced by combining different fields and taking into account the analysis of all approaches to establish a united, unambiguous and uncomplicated system of classification.
... Early interest in S. platensis focused mainly on its potential as a source of protein and vitamins, but recently more attention has been made to study its therapeutic use, and a number of published reports suggest that orally administered phycocyanin or Spirulina exerts potent and versatile anti-inflammatory effects in rodents [3][4][5][6][7]. S. platensis also exhibits antiviral [8], anti-platelet [9], anti-cardiotoxic [10], hypocholesterolemic [11], antinephrotoxic [5], anti-hepatotoxic [6] anti-arthritic [12] and anti-acute allergic rhinitis [13] effects. ...
ABSTRACT
Objective(s): Evidences showed that Spirulina platansis possesses antioxidant and anti- inflammatory properties in-vivo and in-vitro in certain experimental model. Present study aimed to demonstrate the effects of S. platansis powder in collagen induced arthritic rats.
Materials and Methods: In this study five groups (n = 6) of female wistar rats were used as follows: Normal control, Arthritic control, methotrexate treated arthritic rats (0.3 mg kg-1), S. platensis treated arthritic rats (400 mg kg-1) and S. platensis treated arthritic rats (800 mg kg-1). The treatments were started from day 20 to 45, post primary immunization. The change in arthritis score, pain measurement, toe spread expression and total print length, were measured as marker of anti-inflammation in rats.
Results: Our results demonstrated that S. platensis significantly reduced the arthritic activities. These finding indicates that S. platensis has anti-inflammatory effects via modulation of multiple pathways of inflammation. According to the results, the recovery in arthritis score, arthritic pain, toe spread expression and print length were measured in the rat treated with dietary S. platensis (400 mg kg-1) and (800 mg kg-1).
Conclusion: It is suggested that S. platensis inhibits the inflammatory response and oxidative stress. It is because of its anti-inflammatory and anti-oxidant constituents such as phycocyanion, carotenoids, vitamin B1, B2, C, E and other micronutrients.
... Ca-SP from AP has also been studied for its antiviral properties [76][77][78][79]. The spirulina polysaccharides inhibited the replication of several enveloped viruses, including herpes simplex virus, influenza virus, measles virus, mumps virus, human cytomegalovirus, and HIV-1 [78][79][80][81]. However, the mechanism of the antiviral activities of these compounds is poorly understood. ...
The cyanobacterium Arthrospira platensis (Spirulina platensis) is a natural source of considerable amounts of ingredients that are relevant for nutra- and pharmaceutical uses. Different hydrophilic and hydrophobic substances can be obtained by extraction from the biomass. The respective extraction techniques determine the composition of substances in the extract and thus its biological activity. In this short review, we provide an overview of the hydrophilic compounds (phenols, phycobiliproteins, polysaccharides, and vitamins) and lipophilic ingredients (chlorophylls, vitamins, fatty acids, and glycolipids) of Arthrospira platensis. The principal influences of these substances on blood and tissue cells are briefly summarized.
... Spirulina has central neuroprotective effects in rodents [69]. It is also associated with the inhibitory effects against numerous viruses, such as HIV-1, herpes simplex virus 1 and 2 (HSV-1 and HSV-2), human cytomegalovirus (HCMV), influenza type A, measles, and other enveloped viruses [53,[70][71][72][73]. Moreover, it has antimutagenic and anticancer effects [57]. ...
The human immunodeficiency virus (HIV) is one of the most prevalent diseases globally. It is estimated that 37.7 million people are infected with HIV globally, and 8.2 million persons are infected with the virus in South Africa. The highly active antiretroviral therapy (HAART) involves combining various types of antiretroviral drugs that are dependent on the infected person's viral load. HAART helps regulate the viral load and prevents its associated symptoms from progressing into acquired immune deficiency syndrome (AIDS). Despite its success in prolonging HIV-infected patients' lifespans, the use of HAART promotes metabolic syndrome (MetS) through an inflammatory pathway, excess production of reactive oxygen species (ROS), and mitochondrial dysfunction. Interestingly, Spirulina platensis (SP), a blue-green microalgae commonly used as a traditional food by Mexican and African people, has been demonstrated to mitigate MetS by regulating oxidative and inflammatory pathways. SP is also a potent antioxidant that has been shown to exhibit immunological, anticancer, anti-inflammatory, anti-aging, antidiabetic, antibacterial, and antiviral properties. This review is aimed at highlighting the biochemical mechanism of SP with a focus on studies linking SP to the inhibition of HIV, inflammation, and oxidative stress. Further, we propose SP as a potential supplement for HIV-infected persons on lifelong HAART.
... The antiviral activity was not due to a virucidal effect. Herpesvirus infection was inhibited at the initial events (adsorption and penetration) of the viral cycle [84]. ...
Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous
systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious diseases, respectively.
... Furthermore, sulfated polysaccharides are found to be antivirally effective [178], by obstructing the virus adsorption or penetration [179]. Aqueous extracts of two species of Arthrospira, S. platensis, and A. maxima were reported to have antiviral activity [180]. Allo-phycocyanin, the blue pigment/compound extracted from A. platensis, was seen inhibiting apoptosis and interferes with the viral replication at an early stage [181]. ...
Recently there had been a great interest in biologically synthesized nanoparticles (NPs) as potential therapeutic agents. The shortcomings of conventional non-biological synthesis methods such as generation of toxic byproducts, energy consumptions, and involved cost have shifted the attention towards green syntheses of NPs. Among noble metal NPs, gold nanoparticles (AuNPs) are the most extensively used ones, owing to the unique physicochemical properties. AuNPs have potential therapeutic applications, as those are synthesized with biomolecules as reducing and stabilizing agent(s). The green method of AuNP synthesis is simple, eco-friendly, non-toxic, and cost-effective with the use of renewable energy sources. Among all taxa, cyanobacteria have attracted considerable attention as nano-biofactories, due to cellular uptake of heavy metals from the environment. The cellular bioactive pigments, enzymes, and polysaccharides acted as reducing and coating agents during the process of biosynthesis. However, cyanobacteria-mediated AuNPs have potential biomedical applications, namely, targeted drug delivery, cancer treatment, gene therapy, antimicrobial agent, biosensors, and imaging.
Graphical abstract
... [40,41] The effective inhibitory dose (ED 50 ) of Spirulina against HSV-2 is 50%, and <20% for adenovirus. [42] The polysaccharides found in Spirulina extract can act as effective antiviral agents, have low anticoagulation activity, a long half-life in blood (approximately 150 min), and dose-dependent bioactivity. [43] In a 6-month study of HIV-1-infected patients, 82 participants received 10 g of Spirulina per day, along with antiretroviral therapy (ART) and balanced nutrition, compared with 87 participants who received ART In old mice, spirulina exhibited antimicrobial action against pathogenic gut bacteria, thereby altering the bacteroides/ fermicutes ratio, with increased levels of roseburia and lactobacillus (otherwise seen in lower quantities with consumption of a high-fat diet) leading to reduced hepatic inflammation and NASH progression Neyrinck et al., 2017 [25] In rats fed a high-fat diet, spirulina improved lipid metabolism and reduced fatty liver changes by upregulating AMPK-α and downregulating HMG-CoA pathway, by increasing specific beneficial bacteria like prevotella and SCFA producers in colon ...
... The selectivity index (IS) indicates the safety of using the plant extract, and in order to assess how potent the extract is compared to the commercial antiviral ribavirin, the relative potency, calculated in Table 2. Regarding the results of the antiviral tests, all the extracts presented levels of viral inactivation superior to ribavirin, and microalgae showed a dosedependent effect. Also, to evaluate the organic extracts obtained in [90]. In different phases of the four microalgae growth analyzed, it was possible to select the best microalgae growth moment for the obtention of biomass with antiviral activity against MAYV. ...
Mayaro fever, as it is called the disease caused by the Mayaro virus (MAYV), which presents symptoms similar to those of dengue and Zika fevers such as fever, rash, and arthralgia. Once the disease is detected, the treatment is still non-specific since up to the moment there is no therapy capable of curing. Historically, the most affected areas by Mayaro infections are bordered by the Amazon State, or located in the Amazon forest, North of Brazil. Moreover, researches have detected three confirmed cases in Rio de Janeiro, Southeastern Brazil. Many natural compounds from microalgae have attracted special attention owing to their broad spectrum of biological activities and they are called biopharmaceuticals. In this work, we performed a technological mapping aiming to prospect microalgae applied to Biopharmaceuticals. From this study, four strains of microalgae prospected were cultured and their antiviral activity was assayed in vitro against MAYV. The cell viability tests were performed on VERO cells (Verda Reno Cells) to evaluate the cytotoxicity of the extracts by CC50 notation and the inactivation capacity of the MAYV as measured by TCID50. The results showed that all the microalgae strains presented anti-Mayaro activity and the relative potency was superior to ribavirin, the commercial antiviral. Also, the preliminary characterization by TLC and NMR ¹H analysis indicated in the extract composition terpenoid molecules and the majority presence of unsaturated aliphatic molecules.
... Several studies reported that water extract of spirulina revealed antiviral activities, and it is due to the presence of various active chemical constituents which are present in spirulina [37]. Spirulina maxima have antiviral action against type 2 herpes simplex virus [38]. It is reported that Calcium spirulan inhibit the replication of the virus. ...
Oxy+ is a natural source of arthrospira found in nature, used as a dietary supplement and manufactured in Aruba for lifefactors. Arthrospira contains good quality of proteins, sulfated polysaccharides, γ-linoleic acid, along with an array of carotene and phytopigments, vitamins, and minerals which are reported to be antioxidant, immunomodulator, antihyperglycemic, antidyslipidemic, cardioprotective, hepatoprotective, antiviral, anticancerous, antihypertensive, anti-inflammatory, analgesic, neuroprotective and renoprotective activities. Several studies have shown arthrospira, and active ingredients of it revealed various pharmacological activities. It can be used for the management of various ailments such as diabetes, dyslipidemia, obesity, hypertension, cancer, arthritis, osteoarthritis, autoimmune disorders, etc. This review attempts to explore the hidden benefits of Oxy+ (arthrospira).
... In fact, a clear negative correlation between population densities of Arthrospira and Chlorella has been previously reported, and cyanobacterial release of compounds with antibiotic/allelopathic effects on other microalgae as chlorophytes and diatoms was suggested [26,69]. Presence of these bioactive compounds has been also reported for Arthrospira extracts used against bacteria, fungi and viruses [70,71]. Meanwhile, the increased alkalinity and pH along the R phase (pH > 10.1, mean 10.56; Figure 1 and Table 2) most likely prevented the later appearance of Chlorella and other biological contaminants [19,26,64]. ...
Microalgae cultivation is a promising alternative to traditional agriculture in arid—semi-arid areas. The aim of this study is to assess the viability of long-term cultivation of native Arthrospira platensis in Gran Canaria. Maximum culture productivity (0.08 g/L/day) and optimal concentration range (0.6–0.9 g/L) were firstly determined in 8000 L raceway under a greenhouse. Afterwards, a stable productivity of 0.06 g/L/day (6.0 g/m2/day) was obtained by reusing the culture medium during 26 days of cultivation, with consistent biomass biochemical composition. Outdoor temperature and daily solar irradiation ranged between 17.9–30.7 °C and 79.2–274.8 W/m2, while culture pH and salinity were in the range 9.42–10.77 and 11.2–14.9 g/L, respectively. Protein (>60%), potassium (1.8 g/100 g) and C-phycocyanin (7.2%) content is in the high-range of commercial Spirulina, which makes BEA 1257B promising for food and extraction of natural pigments/antioxidants. The dried biomass complies with international standards for human consumption, because of low heavy metal content and no pathogens presence. Product quality can be improved by reducing ash (≃12%) and sodium (1.5%) content through biomass washing optimization and/or further dewatering step. Other microorganisms can be prevented by high alkaline conditions and mild chemical treatments. These results pave the way for a sustainable microalgae-based blue bioeconomy in the Canary Islands.
... An inhibitory effect was recorded on both viral reproduction and infectious capacity 18 . Spirulina maxima showed an antiviral activity against herpes simplex virus type 2 as reported by Hernandez-Corona et al., 19 , who mentioned that methanol-water extract (3:1) have the greatest activity which may be due to the polar substances in the extract. It was suggested that the negatively charged sulfated polysaccharides interacted with positively charged cell surface of the virus so preventing its penetration to the host cell 20 . ...
Aim and objective: The discovery and development of new natural antiviral compounds which exhibit various antiviral activities are required. The aim of this investigation is to assess the potential use of the red seaweed Asparagopsis taxiformis as a new source of anti H 5 N 1 agent. Methods: The seaweed was collected from Marsa Matrouh, Mediterranean Sea, Egypt during spring season, the effects of successive extracts and the pure compounds from the investigated alga on H 5 N 1 virus were performed using plaque reduction assay. In addition, the mechanism of action of promising extract on the virus adsorption and replication was determined. Chromatographic and spectroscopic analyses were used for the identification of chemical structure of active compound(s) isolated from the studied seaweed. Results: The obtained results showed that petroleum ether and water algal extracts exhibited high antiviral activity (>99.9%) and the mode of action of extracts was not correlated with virus replication but with its adsorption process.The isolated pure compound was identified as 6-methyl-Δ 22-stigmasterol-2, 3 di acetate and its antiviral activity (for H 5 N 1)was tested. Pure compound showed antiviral activity reached 56% at 100 µg/ml. Conclusion: The obtained results suggests that crude extracts and isolated active compound from A. taxiformis has the capacity to protect people against pandemic H 5 N 1 preventing virus adsorption to the human host cells. Recommendation for testing the extracts and pure compounds from the studied seaweed as potential inhibitor of COVID-19.
... It also contains vitamins, pigments, i.e. chlorophylla (Chl-a), phycobiliproteins and carotenoids (Cohen 1997), trace elements and minerals that give it different biological properties (El-Baky et al. 2008). Studies and experiments conducted on A. platensis have shown multiple therapeutic effects that include immunomodulation (Abdel-Daim et al. 2015;Wu et al. 2016;Finamore et al. 2017), anticancer (Abu Zaid et al. 2015;Oh et al. 2011;Shanb et al. 2012), antioxidant (Abu Zaid et al. 2015;Wu et al. 2016;Finamore et al. 2017), antiviral (Hernandez-Corona et al. 2002), antibacterial (Ozdemir et al. 2004;Kaushik & Chauhan 2008;Finamore et al. 2017) and probiotic activity (Dola et al. 2009) as well as beneficial effects on wound healing (Syarina et al. 2015;Bari et al. 2017), malnutrition (Kazuya et al. 2014), hyperlipidaemia (Iwata et al. 1990;Ponce-Canchihuamán et al. 2010) and diabetes (Ponce-Canchihuamán et al. 2010). Arthrospira platensis has also been approved by the Food and Drug Administration (FDA) as a food, or food supplement, without risk to human health. ...
2021): Alternative culture media and cold-drying for obtaining high biological value Arthrospiraplatensis (Cyanobacteria), Phycologia, ABSTRACT Arthrospira platensis is a source of proteins, polysaccharides, polyunsaturated fatty acids (in tiny amounts) and phenolic components that give it different biological properties. The type of nutrients present in the culture medium can influence the microalga metabolism and, consequently, the growth, composition and content of nutrients, bioactive compounds and biological properties. In this work, A. platensis was cultivated in the laboratory using six culture media (Zarrouk as a standard medium, and Media 1-5), containing different nitrogen sources, and subsequently harvested and dried by freeze-drying or cold-drying. Medium 4, with KNO 3 as nitrogen source, proved to optimize the productivity of A. platensis (with a maximum yield of 1.34 ± 0.08 g l-1 , better than the Zarrouk medium), to maximize protein synthesis (up to 70% w/w) and to increase the antioxidant activity. Conversely, Medium 3, containing KNO 3 and NH 4 NO 3 , was the best to optimize carbohydrates and lipids (up to 30% w/w and 2% w/w, respectively). Both Media 3 and 4 were able to increase chlorophyll-a and carotenoid synthesis compared to the other tested media. Cold-drying has proved to be an excellent alternative to the more expensive lyophilization: the content of carotenoids and antioxidant components was better preserved. This research has shown that low-cost media and cold-drying can be a promising strategy for obtaining a high biological value product, usable in both the pharmaceutical and food sectors, reducing production times and costs. ARTICLE HISTORY
... Due to its high content of proteins (mainly phycocyanin and allophycocyanin), vitamins, amino acids, minerals, and essential fatty acids, it has been the object of several pharmacological studies [16]. Am has been reported as having anti-inflammatory, immunostimulatory, antiviral, and antioxidant activity [17][18][19][20], as well as producing anti-hepatotoxic and anti-nephrotoxic effects and improving vascular reactivity [21][22][23]. These effects have been related to the antioxidant activity of Am, while others are attributed to some of its active ingredients, such as phycobiliproteins, which decrease oxidative stress [19,24]. ...
... It was reported that Spirulina could inhibit viral replication by blocking replication [78]. Hernández-Corona et al. [79] found that Spirulina inhibited the viral cell penetration and replication in a virus disease named herpes simplex virus type-1 (HSV-1). It was reviewed that the antiviral features of Spirulina are belonged to acidic polysaccharides extract such as calcium spirulina. ...
Natural antioxidant compounds have different mechanisms of treatment and prevention against various diseases due to their richest ingredients. There are several antioxidants used today, such as phytogenic ingredients, flavonoids, capsaicin, spirulina, beta-glucan, polyphenol etc. Besides the outbreak of diseases, the ability to scavenge oxidative conditions of the natural antioxidants have been notably important. Thereby, therapeutic strategies of diseases have been interested by researchers. Try to seek a kind of effects of natural antioxidants to various diseases, especially viral or pandemic diseases are being important nowadays. This chapter we’ll mention about how to viral or pandemic disease’s effects on oxidative status in both animals and humans, and what kind of phytochemical ingredients would be a positive effect on. At the same time, the latest advances about these natural antioxidant compounds and pharmaceuticals will be critically highlighted and discussed with newest literatures.
... In addition, cyanobacteria may have cytotoxic effects as well. A number of cyanobacterial species have been located as sources of antiviral compounds against a number of viruses like herpes viruses, and HIV-1 (Hern andez- Corona et al., 2002;Kanekiyo et al., 2007;Lopes et al., 2011;Neilan et al., 1999;Rechter et al., 2006;Surakka et al., 2005;Teneva et al., 2003;Zainuddin et al., 2002). There are no numerous cases of antiviral compounds from cyanobacteria, as just a few articles highlighted the impact of cyanobacteria as a promising source of antiviral drugs, especially for coronaviruses. ...
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
... Due to the emergence of drug-resistant Herpes simplex strains, several studies have focused on the search for alternatives to synthetical acyclovir in the prevention and treatment of Herpes simplex virus (HSV) 1 and 2. For instance, hot water extract of A. maxima provided EC 50 of 0.069 (Yakoot and Salem 2012) mg.mL −1 against HSV-2. The authors then attributed this antiviral activity to high polar compounds (Hernández-Corona et al. 2002). In a second study, phosphate buffer extract of A. fusiformis showed a viral infection inhibition almost as high as acyclovir (85% against 99%) during the intracellular replication period (Sharaf et al. 2013). ...
A race is currently being launched as a result of the international health situation. This race aims to find, by various means, weapons to counter the Covid-19 pandemic now widespread on all continents. The aquatic world and in particular that of photosynthetic organisms is regularly highlighted but paradoxically little exploited in view of the tremendous possibilities it offers. Computational tools allow not only to clear the existence and activity of many molecules but also to model their relationships with receptors identified in potential hosts. On a routine basis, our laboratory carries out a research activity on functionalities of molecules derived from algae using in silico tools. We have implemented our skills in algae biology and in modeling, as tests in order to identify molecules expressed by the genus Arthrospira showing an antiviral potential and more particularly anti-SARS-CoV-2. Using consensus docking and redocking with Autodock Vina and SwissDock, we were able to identify several promising molecules from Arthrospira: phycocyanobilin, phycoerythrobilin, phycourobilin, and folic acid. These four compounds showed reliable binding energies comprised between - 6.95 and - 7.45 kcal.mol-1 in Autodock Vina and between - 9.285 and - 10.35 kcal.mol-1 with SwissDock. Toxicity prediction as well as current regulations provided promising arguments for the inclusion of these compounds in further studies to assess their ability to compete with the SARS-CoV-2/ACE2 complex both in vitro and in vivo.
Supplementary information:
The online version contains supplementary material available at 10.1007/s10811-021-02372-9.
... In such a case, higher infectious titers would be measured than induced by a fresh extract. Therefore, based on previous studies (Hayashi et al. 1993;Hernández-Corona et al. 2002a;Santoyo et al. 2012) and since we assumed that 1 h is sufficient for the virus to enter the cells, further experiments were carried out without constant virus exposure. Thus, to remove unabsorbed viruses after the initial infection phase the infectious supernatant of all samples and also the supernatant of the replication controls was discarded after inoculation. ...
Microalgae often stand out for their high biodiversity as well as their associated large number of potent bioactives. Therefore, they are interesting candidates as possible sources of antiviral substances, e.g. against cyprinid herpesvirus 3 (CyHV-3). Although this virus leads to high mortalities in aquacultures, there is no treatment available yet. Hence, ethanolic extracts produced with accelerated solvent extraction from six microalgal species (Arthrospira platensis, Chlamydomonas reinhardtii, Chlorella kessleri, Haematococcus pluvialis, Nostoc punctiforme and Scenedesmus obliquus) were examined in this study for inhibitory effects on viral replication. An inhibition of the in vitro replication of CyHV 3 in common carp brain cells could be confirmed for all six species, with the greatest effect for the C. reinhardtii and H. pluvialis extracts. At still non-cytotoxic concentrations viral DNA replication was reduced by over 3 orders of magnitude (> 99.9 %) each compared to the untreated replication controls, while the virus titers were at or even below the limit of detection. When pre-incubating cells and virus with C. reinhardtii and especially H. pluvialis extracts before inoculation, the reduction of viral DNA and virus titer was even stronger. Based on these results, an intervention in the initial replication steps like viral adsorption or membrane fusion is assumed. Moreover, a protection mechanism preventing the production of viral proteins and the assembly of mature virions is also possible. All in all, the results show that microalgae are a very promising source of natural antiviral substances against CyHV-3.
... Cyanobacterial and microalgal allelochemicals can also be used in medicine and the pharmaceutical industry. The antimicrobial, antifungal, and antiviral activities of allelochemicals produced by different cyanobacteria (i.e., Fischerella sp., Lyngbya sp., Phormidium sp., Pseudanabaena sp., Spirulina sp., and Scytonema sp.) as well as microalgae (Porphyridium sp., Rhodella sp., Chlorella sp., and Gyrodinium sp.) were demonstrated (Gustafson et al., 1989;Patterson and Boils, 1995;Hagmann and Jüttner, 1996;Oufdou et al., 2001;Hernández-Corona et al., 2002;Garima et al., 2013;Liu et al., 2016). Moreover, Martins et al. (2008) and Costa et al. (2014) showed that some picocyanobacteria from the genera Cyanobium, Synechococcus, and Synechocystis were able to induce cytotoxic effects in human cancer cell lines. ...
Allelopathy is widespread in marine, brackish, and freshwater habitats. Literature data indicate that allelopathy could offer a competitive advantage for some phytoplankton species by reducing the growth of competitors. It is also believed that allelopathy may affect species succession. Thus, allelopathy may play a role in the development of blooms. Over the past few decades, the world’s coastal waters have experienced increases in the numbers of cyanobacterial and microalgal blooming events. Understanding how allelopathy is implicated with other biological and environmental factors as a bloom-development mechanism is an important topic for future research. This review focuses on a taxonomic overview of allelopathic cyanobacteria and microalgae, the biological and environmental factors that affect allelochemical production, their role in ecological dynamics, and their physiological modes of action, as well as potential industrial applications of allelopathic compounds.
An emerging concern for the environment, especially marine systems, is microplastics; these plastics with a micro or nano size interact with their environment causing terrible damages; algae are the first barrier encountered by microplastics; this induces a double impact: in one side algae can transform microplastics and reduce their pollution impact, and in another side microplastics can affect algae population but most importantly can induce changes in their composition and the quality of the nutrient and active ingredients produced by algae; these changes are drastic but could be in each way negative or positive.
This review will highlight the effects of microplastic pollution on algae population, nutraceutical, and active ingredients content; the different classes of algae will be defined and their content and effect presented to be able to make the connection between the presence of microplastics in algae environment and the quality and quantity of their content of nutrients and active ingredients.
Aquaculture is an important sector within animal production worldwide. Despite its rapid growth in recent decades, it has encountered certain challenges in the availability of raw materials for feed production, the appearance of epidemic outbreaks, and the overall environmental sustainability of the sector. One emerging strategy for addressing these challenges is the development and use of feed additives. These additives are products, not raw materials or premixes, intentionally added to feed to achieve an effect on the feed itself, on animals, on food products obtained from animals, or on the environment.
The research carried out on this subject in recent decades has allowed the development of a large number of additives that can currently be used in aquaculture, although their use and regulation are more advanced in terrestrial farmed species. Among the most used additives, there are pro- and prebiotics, enzymes, vitamins, amino acids, fatty acids, minerals, and other functional compounds obtained from plants, bacteria, micro and macroalgae, fungus, or other animals (i.e., insects or crustaceans).
In accordance with the safety demands of consumers and with the strategies developed worldwide to reduce the climate and environmental footprint of food production, the current trend is toward the development of increasingly sustainable feed additives, of natural origin and not toxic. Its effects on aquaculture species are being studied through physiology, immunology, and different –omics using cutting-edge techniques. In order to analyze all these advances in feed additives, this chapter gathers the main research in this regard, emphasizing natural additives or those that favor sustainability. In addition, recent changes in legislation concerning development and use of feed additives are analyzed, as well as future perspectives on their use as key tools to increase the sustainability of the food sector.
Background-Freshwater microalgae called spirulina have been consumed for many years as a dietary supplement. This algae possesses a diversified concentration of nutrients and has been known as a wonder medicine due to its many applications. It promotes immunity and resistance to several illness. Spirulina possesses a high content of proteins, essential amino acid, lipids, polysaccharides, dietary minerals, vitamins, and fatty acids which is responsible for its pharmacological action like antimicrobial effect, anticancer and metaloprotective effect, potent immunostimulant and antioxidant effects. Methodology-The experimental analysis and data reported on the species of spirulina were reviewed since the year 2005 to 2021.Various database were used as article source like Medline and Pubmed and literature review was done by using the key words spirulina, habitat, species, pharmacological action, toxicities and traditional uses. Result-This article provides an outline of this algae's basic biochemical makeup before moving on to its potential uses in medicine. The fundamental description of the illness, the mechanism of harm, the specific Spirulina spp. content for therapy, in vivo and/or in vitro usage, variables related with therapeutic role, challenges encountered, and benefits are presented for each application.
Arthrospira platensis is a filamentous cyanobacterium of the class Cyanophyceae and is the most cultivated photosynthetic prokaryote. It is used in the pharmaceutical sector, medicine and the food industry. It has a rich micro- and macro-element composition, containing proteins, lipids, carbohydrates, essential amino acids, polyunsaturated fatty acids, minerals and raw fibers. It is a commonly used ingredient in food products and nutritional supplements. The wide range of biologically active components determines its diverse pharmacological properties (antioxidant, antidiabetic, antimicrobial, antineoplastic, antitumor, anti-inflammatory, photoprotective, antiviral, etc.). This review summarizes research related to the taxonomy, distribution and chemical composition of Arthrospira platensis as well as its potential application in the food and pharmaceutical industries. Attention is drawn to its various medical applications as an antidiabetic and antiobesity agent, with hepatoprotective, antitumor, antimicrobial and antiviral effects as well as regulatory effects on neurodegenerative diseases.
Implant Destekli Sabit Protezlerde Protetik Başarısızlık Nedenleri (Derleme)
Background:
Spirulina (Arthrospira maxima) hot water extracts such as calcium spirulan (Ca-SP) have demonstrated antiviral effects against herpes simplex virus (HSV), human immunodeficiency virus-1 (HIV-1), and influenza virus infections. There is no prior evidence suggesting the anti-viral activity of the spirulina hot water extract against respiratory syncytial virus (RSV).
Purpose:
There are currently no effective antivirals available to treat RSV infection. Therefore, the development of safe and novel anti-RSV drugs is urgent and necessary. The aim of this work was to demonstrate the anti-RSV activity of spirulina hot water extracts and determine the potential mechanism of action.
Methods:
Cytotoxicity and anti-RSV activity of spirulina hot water extracts were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutralization assays, respectively. Potential mechanisms and components were assessed using time of addition, attachment, internalization, pull-down assays, and composition analysis.
Results:
The polysaccharide-enriched high-molecular weight fraction (>100 kDa, SHD1) had a high total sugar content, with rhamnose accounting for approximately 60 mol% of total monosaccharides. The main glycosyl linkages included 3-, 4-, and 2,3-rhamnopyranosyl linkages. All spirulina hot water extracts showed no toxicity toward human epithelial type 2 (HEp-2) cells but demonstrated anti-RSV activity. The SHD1 had a half maximal effective concentration (EC50) of 0.0915 mg/ml and a selective index (SI) of >261.5 against RSV. SHD1 significantly reduced viral yield in a dose-dependent manner during the RSV attachment stage. SHD1 disrupted RSV internalization and inhibited RSV attachment (G) protein binding to heparan sulfate receptors on the host cell surface, thus preventing RSV attachment and entry.
Conclusion:
SHD1 serves as an effective candidate for novel drug development against RSV infection.
Polysaccharides are essential macromolecules for living organisms, they are widely found in plants, animals, microorganisms, and algae. However, marine polysaccharides of microalgal origin have gained prominence over the last few years for their variety of applications in food, cosmetics, and especially health. The versatility of its applications is due to the derived complex chemical structures which come from its types of monosaccharide constituent, conformation, and the presence of substituent groups, especially the sulfate group. These facts contribute to the microalgae are promising for polysaccharides production. Some challenges related to extraction, identification, and purification have yet to be overcome, however, microalgae prove to be a potential source for the production of this class of compounds. In this sense, this review presents a comprehensive description of the production of microalgae polysaccharides, aspects related to chemical structure, rheological and functional characteristics, applications, and strategies for determination, in addition to a brief description of the main challenges for the use of these macromolecules. In summary, the results presented and discussed here can further elucidate the full potential of microalgae polysaccharides for different application purposes, in addition to providing guidance for the main hot spots to be considered in future research in this scientific field.
There is a current tendency towards bioactive natural products that can be used in different areas such as food, pharmaceutical, and biomedical. In the last decades, the polysaccharides have attracted an increasing interest because of the potent nontoxic effects, therapeutic properties, and the diversified range of applications. Polysaccharides are complex and heterogeneous macromolecules, constituted of different monosaccharides, and in some cases of glucuronic acid and sulphate groups. Polysaccharides with biological activity can be derived from plants, animals and microorganisms, especially microalgae. Microalgae are considered one of most promising source of these compounds that have already proved to have several important biological properties. In this sense, our objective is to elucidate the use of bioactive polysaccharides from microalgae in biomedical applications, emphasizing the biological activity of these compounds. Furthermore, the microalgal biomass production systems and polysaccharides extraction methods were presented and discussed.
In recent years, the increasing concern about human health well-being has strongly boosted the search for natural alternatives that can be used in different fields, especially in biomedicine. This has put microalgae-based products in evidence since they contain many bioactive compounds, of which polysaccharides are attractive due to the diverse physicochemical properties and new or improved biological roles they play. Polysaccharides from microalgae, specially exopolysaccharides, are critically important for market purposes because they can be used as anti-inflammatory, immunomodulatory, anti-glycemic, antitumor, antioxidant, anticoagulant, antilipidemic, antiviral, antibacterial, and antifungal agents. Therefore, to obtain higher productivity and competitiveness of these naturally available compounds, the cultivation parameters and the extraction/purification processes must be better optimized in order to bring perspectives for the exploitation of products in commercial and clinical practice. In this sense, the objective of the present review is to elucidate the potential biomedical applications of microalgae-derived polysaccharides. A closer look is taken at the main polysaccharides produced by microalgae, methods of extraction, purification and structural determination, biological activities and their applications, and current status.
Chlorella spp., Spirulina spp., and fucoidan dry powders, are commercialized as food supplements and are considered safe for human consumption. Their broad-spectrum antiviral properties have been studied, however, their effect against SARS-CoV-2 remains unknown. We investigated the potential antiviral activity of three algae powders: Chlorella vulgaris, Spirulina máxima and fucoidan purified from marine brown algae Sargassum spp. against SARS-CoV-2 infection in vitro. Vero cells were incubated with 70 μg/ml of each algae powder and either 50 or 100 TCID50/ml of SARS-CoV-2. Chlorella powder inhibited SARS-CoV-2 infection; viral RNA was signifcantly reduced in supernatants at 24, 48, 72, and 96 hrs post-infection, the highest difference in viral load (8000-fold) was observed after 96 hrs. Spirulina maxima powder partially inhibited SARS-CoV-2 infection since no cytopathic effect was observed in 87.5% of infected cultures and viral RNA decreased 48 hrs after infection, reaching a 250-fold difference at 72hrs. In conclusion, our preliminary in vitro assays suggest that C. vulgaris and S. máxima dry algae, may potentially be used to fight COVID-19.
The present global COVID-19 pandemic caused by the noble pleomorphic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a vulnerable situation in the global healthcare and economy. In this pandemic situation, researchers all around the world are trying their level best to find suitable therapeutics from various sources to combat against the SARS-CoV-2. To date, numerous bioactive compounds from different sources have been tested to control many viral diseases. However, microbial metabolites are advantageous for drug development over metabolites from other sources. We herein retrieved and reviewed literatures from PubMed, Scopus and Google relevant to antiviral microbial metabolites by searching with the keywords "antiviral microbial metabolites," "microbial metabolite against virus," "microorganism with antiviral activity," "antiviral medicine from microbial metabolite," "antiviral bacterial metabolites," "antiviral fungal metabolites," "antiviral metabolites from microscopic algae' and so on. For the same purpose, the keywords "microbial metabolites against COVID-19 and SARS-CoV-2" and "plant metabolites against COVID-19 and SARS-CoV-2" were used. Only the full text literatures available in English and pertinent to the topic have been included and those which are not available as full text in English and pertinent to antiviral or anti-SARS-CoV-2 activity were excluded. In this review, we have accumulated microbial metabolites that can be used as antiviral agents against a broad range of viruses including SARS-CoV-2. Based on this concept, we have included 330 antiviral microbial metabolites so far available to date in the data bases and were previously isolated from fungi, bacteria and microalgae. The microbial source, chemical nature, targeted viruses, mechanism of actions and IC 50 /EC 50 values of these metabolites are discussed although mechanisms of actions of many of them are not yet elucidated. Among these antiviral microbial metabolites, some compounds might be very potential against many other viruses including coronaviruses. However, these potential microbial metabolites need further research to be developed as effective antiviral drugs. This paper may provide the scientific community with the possible secret of microbial metabolites that could be an effective source of novel antiviral drugs to fight against many viruses including SARS-CoV-2 as well as the future viral pandemics.
SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2′s spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein's RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.
Spirulina is a microscopic and filamentous cyanobacterium that has a long history of use as a safe functional food. It is commercially produced in large outdoor ponds under controlled conditions. Here we have summarized available information concerning the human clinical potential and applications of Spirulina, as well as clinical data related to the safety and ikside effects of Spirulina. Potential health benefits of Spirulina are mainly due to its chemical composition, which includes proteins, carbohydrates, essential amino acids, minerals (especially iron), essential fatty acids, vitamins, and pigments. In this respect, three major bioactive components of Spirulina, the protein phycocyanin, sulfated polysaccharides, and γ-linolenic acid, seem to play significant roles in imparting improved human body functions. Furthermore, experimental evidence supports the immunomodulation and antiviral effects of Spirulina supplementation. Moreover, the available clinical evidence does not indicate a serious risk to health or other public health concerns due to Spirulina.
A series of chemically oversulphated galactosaminoglycans (SO3H:COOH ratio > or = 2) were tested in vitro as antiviral agents against human immunodeficiency virus type 1 (HIV-1), the aetiological agent of AIDS, and against herpes simplex virus type 1 and human cytomegalovirus, two agents responsible for opportunistic infections in HIV-infected people. The oversulphated derivatives displayed an increase in activity ranging from one to four orders of magnitude against the three viruses, as compared to the natural parent compounds (SO3H:COOH, ratio approx. 1). The antiviral activity of these polyanions appears to be favoured by a high degree of sulphation and a high molecular mass. An oversulphated dermatan, with a SO3H:COOH ratio of 2.86 and molecular mass of 23.2 kDa, was the most potent anti-HIV-1 compound (EC50 0.04 microgram/ml). A second oversulphated dermatan, with a SO3H:COOH ratio of 2.40 and molecular mass of 25 kDa, displayed the highest activity against HSV-1 (EC50 0.01 microgram/ml). An oversulphated chondroitin, with a SO3H:COOH ratio of 2.80 and molecular mass of 17.3 kDa, was the strongest anti-HCMV agent (EC50 0.4 microgram/ml). In view of the absence of the side-effects typical of heparin-like compounds, a combination of these derivatives could have therapeutic potential.
A novel fucan sulfate (Hor-1) was isolated from the hot water extract of an edible brown alga, Sargassum horneri (Turner) C. Agardh. The fucan sulfate was revealed to have sugar linkage types, sulfate content and uronic acid content different from those of sodium hornan (Na-HOR), another fucan sulfate isolated from this alga. However, it exhibited inhibitory activity against replication of herpes simplex virus type 1 with similar potency to Na-HOR.
The effects of dietary Spirulina platensis on chicken macrophage phagocytic function and nitrite production were examined. Day old broiler (meat-type) chicks were randomly assigned to various pens of electrically heated wire batteries. Dietary treatment groups included a basal diet with no dietary Spirulina added, and three additional groups with 0.5, 1.0 and 2.0% dietary Spirulina. Feed and water were provided for ad libitum consumption from one day of age. Sephadex-elicited macrophages were harvested at 14, 35 and 42 days of age. Phagocytosis assay was performed by co-incubating sheep red blood cells (SRBC) with the adherent macrophage monolayers. For nitrite quantification, macrophage cultures from various dietary treatment groups were stimulated in the presence or absence of 1 microg/mL of Escherichia coli lipopolysaccharide. These culture supernatant fractions were then tested for nitrite levels using the Greiss reagent technique. All Spirulina dietary group macrophages exhibited an enhanced phagocytic activity in terms of overall phagocytic percentage (range = 28 to 39% versus 24 to 25% in the basal group) and the average number of SRBC per phagocytic macrophage (range = 2.2 to 3.6 versus 1.8 to 2.5 in the basal group). This increase was linear with each incremental increase of dietary Spirulina. While LPS-induced nitrite levels in macrophages from basal diet group ranged from 60 to 278 microM over the three developmental ages, these levels in all Spirulina dietary groups were significantly higher (0.5% group range = 198 to 457 microM; 1.0% group range = 161 to 359 microM and 2.0% group range = 204 to 420 microM. These data clearly show that Spirulina platensis feeding upregulates macrophage phagocytic as well as metabolic pathways leading to increased nitric oxide synthase activity. These findings therefore imply that Spirulina platensis may enhance the functions of mononuclear phagocytic system thereby increasing the disease resistance potential in chickens.
Rhamnan sulfate (RS), a natural sulfated polysaccharide isolated from Monostroma latissimum, showed potent inhibitory effects on the virus replication of herpes simplex virus type 1 (HSV-1), human cytomegalovirus (HCMV), and human immunodeficiency virus type 1 (HIV-1) in vitro. The antiviral action of RS was not only due to the inhibition of virus adsorption, but also might involve the later steps of viral replication in host cells on the basis of the results of time-of-addition experiments. Furthermore, RS and 3'-azido-3'-deoxythymidine (AZT) were synergistic in their anti-HIV-1 activities. These data indicate that RS is a potent antiviral substance against HSV-1, HCMV, and HIV-1.
The water-soluble extract of Spirulina platensis achieved a dose-dependent inhibition of the replication of herpes simplex virus type 1 (HSV-1) in HeLa cells within the concentration range of 0.08–50 mg/mL. This extract proved to have no virucidal activity and did not interfere with adsorption to host cells. However, the extract affected viral penetration in a dose-dependent manner. At 1 mg/mL the extract was found to inhibit virus-specific protein synthesis without suppressing host cell protein synthesis if added to the cells 3 h before infection. In an in vivo experiment food containing the extract effectively prolonged the survival time of infected hamsters at doses of 100 and 500 mg/kg per day.
A water soluble substance was isolated from a Chinese herb, Prunellavulgaris, by hot water extraction, ethanol precipitation and gel permeation column chromatography. Chemical tests showed that the substance was an anionic polysaccharide. Using a plaque reduction assay, the polysaccharide at 100 μg/ml was active against the herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), but was inactive against cytomegalovirus, the human influenza virus types A and B, the poliovirus type 1 or the vesicular stomatitis virus. The 50% plaque reduction dose of the polysaccharide for HSV-1 and HSV-2 was 10 μg/ml. Clinical isolates and known acyclovir-resistant (TK-deficient or polymerase-defective) strains of HSV-1 and HSV-2 were similarly inhibited by the polysaccharide. Pre-incubation of HSV-1 with the polysaccharide at 4, 25 or 37°C completely abrogated the infectivity of HSV-1, but pre-treatment of Vero cells with the polysaccharide did not protect cells from infection by the virus. The addition of the polysaccharide at 0, 2, 5.5 and 8 h post-infection of Vero cells with HSV-1 at a multiplicity of infection (MOI) of five reduced the 20 h-yield of intracellular infectious virus by 100, 99, 99 and 94%, respectively. In contrast, a similar addition of heparin showed 85, 63, 53 and 3% reduction of intracellular virus yield, respectively. These results suggest that the polysaccharide may inhibit HSV by competing for cell receptors as well as by some unknown mechanisms after the virus has penetrated the cells. The Prunella polysaccharide was not cytotoxic to mammalian cells up to the highest concentration tested, 0.5 mg/ml and did not show any anti-coagulant activity. In conclusion, the polysaccharide isolated from P. vulgaris has specific activity against HSV and its mode of action appears to be different from other anionic carbohydrates, such as heparin.
A highly sensitive and accurate assay system was developed for in vitro evaluation of anti-herpes simplex virus (anti-HSV) agents using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and human embryonic lung fibroblast (MRC-5) cells. This assay system was found to be highly sensitive for both HSV-1 and -2. Confluent MRC-5 cells were infected with either HSV-1 KOS strain or HSV-2 G strain of 25 TCID50 in the presence of various concentrations of test compounds. The optical density of formazan was used to determine cell viability. The EC50 values of acyclovir and several other anti-HSV agents were found to be similar to those obtained by the plaque reduction method. These results indicate that this MTT assay is useful for screening anti-HSV-1 and -2 agents.
The embryotoxic and fetotoxic potential of Spirulina was investigated in mice. The algae was given to pregnant animals at the levels of 0, 10, 20 and 30 g/100 in the diet through days 7-13, 1-13 and 1-19 of gestation. On day 19, the rats were sacrificed, and the uterine horns were examined for live, dead and resorbed fetuses. The live fetuses were weighed and examined for external malformations and either skeletal or visceral abnormalities. With the litter as the unit of analysis and when the total number of fetuses affected was considered, no significant difference was found in the number of resorbed or malformed among groups. These results indicate that the feeding of pregnant mice with algae, up to a dietary level of 30 g/100, did not evoke any signs of embryotoxic effects. The Spirulina levels tested in this study represent exaggeration over any anticipated human consumption.
The algae Spirulina has been considered for use as a supplementary protein to feed and food. Any form of single cell protein destined to this purpose should be previously subjected to detailed toxicological investigations in animals or another experimental models. The present study was therefore designed to determine the teratogenic potential of Spirulina in rats. The algae was administered in the diet at the levels of 0, 10, 20 and 30 g/100 g on days 7-14, 1-14 and 1-21 of gestation. The dams were sacrificed prior to term, and the fetuses examined for external, visceral and skeletal abnormalities. Maternal and fetal weights were not affected. Neither fetotoxicity nor teratogenicity was associated with the dietary ingestion of Spirulina. It is also considered important to extend these studies to other animal species.
Spirulina maxima, an edible micro-organism useful in human nutrition, was examined for its effect on general reproductive performance and for peri- and postnatal toxicity in rats at levels of 0, 10, 20 and 30% (w/w) incorporated into the diet. There was no reduction in body weight gain in males or females and no deaths or clinical signs of toxicity. Treatment was not associated with any adverse effect on any measure of reproductive performance, including male and female fertility and duration of gestation. There was no increase in the number of abnormal pups at caesarean section or at birth. S. maxima consumption did not result in adverse effects on developmental markers of the pups.
The first step of the herpes virus infection is the attachment to heparan sulfate molecules on the cellular membrane. In order to improve the characterization of this phenomenon, we compared the inhibitory effect of six sulfated polyelectrolytes (PE): heparin, heparan, low molecular weight heparin, chondroitin, dextran and protamine on plaque formation by pseudorabies virus (PRV) were compared. The PE with the highest antiherpetic effect was heparin, followed by dextran sulfate. Heparan sulfate, which has been proposed as the initial receptor of herpes virus on the cell surface showed an effect 100-fold lower than heparin. Comparative inhibition curves of heparin and heparan sulfate against three herpes viruses: herpes simplex virus 1 (HSV-1), HSV 2 and PRV showed similar kinetics of inhibition of plaque formation, suggesting these viruses could share similar cell adsorption mechanisms.
A sulfated polysaccharide named calcium spirulan (Ca-SP) has been isolated from a sea alga, Spirulina platensis, as an antiviral component. The anti-human immunodeficiency virus type 1 (HIV-1) and anti-herpes simplex virus type 1 (HSV-1) activities of Ca-SP were compared with those of dextran sulfate (DS) as a representative sulfated polysaccharide. Anti-HIV-1 activities of these agents were measured by three different assays: viability of acutely infected CD4-positive cells, or a cytopathology assay; determination of HIV-1 p24 antigen released into culture supernatants; and inhibition of HIV-induced syncytium formation. Anti-HSV-1 activity was assessed by plaque yield reduction. In addition, their effects on the blood coagulation processes and stability in the blood were evaluated. These data indicate that Ca-SP is a potent antiviral agent against both HIV-1 and HSV-1. Furthermore, Ca-SP is quite promising as an anti-HIV agent because even at low concentrations of Ca-SP an enhancement of virus-induced syncytium formation was not observed, as was observed in DS-treated cultures, Ca-SP had very low anticoagulant activity, and showed a much longer half-life in the blood of mice when compared with that of DS. Thus, Ca-SP can be a candidate agent for an anti-HIV therapeutic drug that might overcome the disadvantages observed in many sulfated polysaccharides. When the role of chelation of calcium ion with sulfate groups was examined by removing calcium or its replacement by sodium, the presence of calcium ion in the molecule was shown to be essential for the dose-dependent inhibition of cytopathic effect and syncytium formation induced by HIV-1.
Bioactivity-directed fractionation of a hot H2O extract from a blue-green alga Spirulina platensis led to the isolation of a novel sulfated polysaccharide named calcium spirulan (Ca-SP) as an antiviral principle. This polysaccharide was composed of rhamnose, ribose, mannose, fructose, galactose, xylose, glucose, glucuronic acid, galacturonic acid, sulfate, and calcium. Ca-SP was found to inhibit the replication of several enveloped viruses, including Herpes simplex virus type 1, human cytomegalovirus, measles virus, mumps virus, influenza A virus, and HIV-1. It was revealed that Ca-SP selectively inhibited the penetration of virus into host cells. Retention of molecular conformation by chelation of calcium ion with sulfate groups was suggested to be indispensable to its antiviral effect.
Spirulina, a unicellular filamentous blue-green alga has been consumed by man since ancient times in Mexico and central Africa. It is currently grown in many countries by synthetic methods. Initially the interest in Spirulina was on its nutritive value: it was found almost equal to other plant proteins. More recently, some preclinical testing suggests it has several therapeutic properties such as hypocholesterolemic, immunological, antiviral and antimutagenic. This has led to more detailed evaluations such as nucleic acid content and presence of toxic metals, biogenic toxins and organic chemicals: they have shown absence or presence at tolerable levels according to the recommendations of international regulatory agencies. In animal experiments for acute, subchronic and chronic toxicity, reproduction, mutagenicity, and teratogenicity the algae did not cause body or organ toxicity. In all instances, the Spirulina administered to the animals were at much higher amounts than those expected for human consumption. On the other hand there is scant information of the effects of the algae in humans. This area needs more research.
An aqueous extract of the blue-green filamentous algae Arthrospira platensis (previously called Spirulina platensis) inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells (LC). Extract concentrations ranging between 0.3 and 1.2 microg/ml reduced viral production by approximately 50% (50% effective concentration [EC50]) in PBMCs. The 50% inhibitory concentration (IC50) of extract for PBMC growth ranged between 0.8 and 3.1 mg/ml. Depending on the cell type used, therapeutic indices ranged between 200 and 6000. The extract inactivated HIV-1 infectivity directly when preincubated with virus before addition to human T-cell lines. Fractionation of the extract revealed antiviral activity in the polysaccharide fraction and also in a fraction depleted of polysaccharides and tannins. We conclude that aqueous A platensis extracts contain antiretroviral activity that may be of potential clinical interest.
The purpose of this study was to evaluate the toxicity of Spirulina maxima, a blue-green alga used as food supplement and food coloring, after 13 weeks of treatment. Groups of ten mice of each sex were given S. maxima in the diet at concentrations of 0 (control), 10, 20 or 30% (w/w) for 13 weeks. The alga ingestion had no effect on behavior, food and water intake, growth or survival. Terminal values in hematology and clinical chemistry did not reveal differences between treated and control groups. However, male and female mice showed significant changes in serum cholesterol levels at 20 and 30% algal concentrations, but a toxic effect of S. maxima was excluded. Post-mortem examination revealed no differences in gross or microscopic findings. Our results show that S. maxima up to high feeding levels did not produce adverse effects in mice after subchronic treatment.
Sulfated polysaccharides exhibit many biological properties such as antiviral and anticoagulant activities. Herein, we report the antiviral activity of sulfated galactans extracted from the red sea-weed Bostrychia montagnei against herpes simplex virus types 1 (strain F and the thymidine kinase-deficient strains Field and B2006) and 2 (strain G). Two crude extracts obtained with cold and hot water as well as some fractions obtained by anion exchange chromatography, inhibited significantly the replication of the different strains of herpesviruses as determined by plaque reduction assays. The inhibitory effect of the compounds studied here took place only when they were added during the adsorption period. They were found to be highly selective antiviral substances, causing no impairment of Vero cell viability. Furthermore, they had no direct inactivating effect on virions by incubation in a virucidal assay. The antiviral activity could be correlated with the molecular weight and sulfate content of the polysaccharides. Although sulfated polysaccharides are generally endowed with anticoagulant properties, the results of the activated partial thromboplastin time and the thrombine time assays indicated that the natural sulfated polysaccharides from Bostrychia montagnei have very low anticoagulant activity, confirming that there is no relation between the antiviral and anticoagulant properties.
Spirulina platensis, planktonic blue-green algae, is gaining increasing attention because of its nutritional and medicinal properties. This microalgae contains phycobiliproteins (phycocyanin and allophycocyanin). Previous reports from our laboratory have shown that a protean extract of S. platensis is a potent free-radical scavenger (hydroxyl and peroxyl radicals) and inhibits microsomal lipid peroxidation. The aim of this study was to purify and characterize phycocyanin of S. platensis. Besides, we tried to demonstrate that one of the main components responsible for this antioxidant activity is a biliprotein phycocyanin. For this purpose, we studied the antioxidant activity of different fractions obtained during the phycocyanin purification process, through the scavenger activity of hydroxyl radical. We also observed that an increase in phycocyanin content was related to an increase in the antioxidant activity in different fractions, and therefore phycobiliprotein phycocyanin is the component mainly responsible for the antioxidant activity.
The dietary administration of 5% Spirulina maxima (SM) during four weeks to diabetic mice, starting one week after a single dose of alloxan, 250 mg/Kg body weight, prevented fatty liver production in male and female animals. The main action of SM was on triacylglycerol levels in serum and liver. There was also a moderate hypoglycemia in male mice. The thiobarbituric acid reactive substances also decreased in serum and liver after SM administration. There was also a decrease in the percentage of HDL in diabetic mice that was reverted by the SM administration. The sum of LDL + VLDL percentages was also partially normalized in diabetic animals by the SM administration. An additional observation was the lower incidence of adherences between the liver and the intestine loops in the diabetic mice treated with SM compared with diabetic mice without SM. Male and female mice showed differences to diabetes susceptibility and response to SM, the female being more resistant to diabetes induction by alloxan and more responsive to the beneficial effects of SM. It is worth future work of SM on humans looking for better quality of life and longer survival of diabetic patients.
To observe polysaccharide of Spirulina platensis (PSp) on the hematopoietic system of mouse and dogs which were damaged by injection of cyclophosphamide (CTX) and 60Co-gamma irradiation.
CTX and 60Co gamma ray were used to induce bone marrow damage, and the experimental animals were ig with different dose of PSp in vivo, after 12-d and 21-d administration, the whole blood cells and nucleated cells in bone marrow were measured, and the DNA in bone marrow were inspected by UV-spectrophotometer.
CTX and 60Co-gamma irradiation induced hemopoietic system damage in mice and dogs, respectively. PSp 30, 60 mg/kg increased the level of the white cells in blood and nucleated cells and DNA in bone marrow in mice but had no effects on red cells and hemoglobins. PSp 12 mg/kg increased the level of red cells, white cells, and hemoglobins in blood and nucleated cells in bone marrow in dogs (P < 0.01), and the effects of PSp 60 mg/kg were better than that of berbamine hydrochloride 60 mg/kg.
PSp has chemo-protective and radio-protective capability, and may be a potential adjunct to cancer therapy.
Lymphocytes are important components of the immune system. Dietary lipids affect the functioning of the immune system. Changes in the lipid composition of the lymphocyte membrane is a case in point. Membrane structural changes are reflected in the altered function of the cell. Lymphocyte proliferation and lymphocyte rosetting are membrane associated phenomena. Ghee, is a clarified butter product, commonly used in the Indian diet. It is rich in saturated fatty acids and also contain oxysterols which are generated on prolonged heating of ghee. Male weanling rats were fed 2.5% (of the total fat levels) of fresh or thermally oxidized ghee for a period of 8 weeks. The control rats were fed groundnut oil. Lipid composition of lymphocytes in ghee fed rats showed changes. In vitro lipid peroxidation of lymphocyte membranes increased by 26% in oxidized ghee fed rats. Na+K+ ATPase activity was decreased in oxidized ghee fed rats (18%). Lymphocyte proliferation was reduced in ghee fed rats (32%), compared to the controls, irrespective of the mitogens used (Con-A or PHA), or the tissue (splenocytes or peripheral blood lymphocytes). Oxysterols present in oxidized ghee are the likely agents inhibiting lymphoproliferation. Rosetting of lymphocytes decreased in the fresh ghee fed rats by 16% and in oxidized ghee fed rats by 25%. Membrane fluidity declined in the oxidized ghee fed rats. It is concluded that feeding ghee results in decreased proliferation of lymphocytes. Also, feeding oxidised ghee results in decreased proliferation of lymphocytes through alterations in the structure of the lymphocyte membranes in the rat.
Numerous reports have revealed an inverse association between consumption of some selective natural products and risk of developing cancer. In the present study the effect of 250 and 500 mg/kg body wt. of Spirulina was examined on drug metabolising phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of 7-week-old Swiss albino mice. The implications of these biochemical alterations have been further evaluated adopting the protocol of benzo(a)pyrene induced forestomach and 7,12 dimethylbenz(a)anthracene (DMBA) initiated and croton oil promoted skin papillomagenesis. Our primary findings reveal the 'Monofunctional' nature of Spirulina as deduced from its potential to induce only the phase II enzyme activities associated mainly with carcinogen detoxification. The glutathione S-transferase and DT-diaphorase specific activities were induced in hepatic and all the extrahepatic organs examined (lung, kidney and forestomach) by Spirulina pretreatment (significance level being from p < 0.05 to p < 0.005) except for the low dose treatment in forestomach. With reference to antioxidant enzymes viz., superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione were increased significantly by both the chosen doses of Spirulina from p < 0.01 to p < 0.005. Chemopreventive response was quantitated by the average number of papillomas per effective mouse (tumor burden) as well as percentage of tumor bearing animals. There was a significant inhibition of tumor burden as well as tumor incidence in both the tumor model systems studied. In the skin tumor studies tumor burden was reduced from 4.86 to 1.20 and 1.15 by the low and high dose treatment respectively. In stomach tumor studies tumor burden was 2.05 and 1.73 by the low and high doses of Spirulina treatment against 3.73 that of control.
Spirulina platensis is a cyanobacterial species that is surmised to potentiate the immune system leading to suppression of cancer development and viral infection. Here, we identified the molecular mechanism of the human immune potentiating capacity of Spirulina by analyzing blood cells of volunteers with pre and post oral administration of hot water extract of Spirulina. NK functions represented by IFN gamma production and cytolysis were enhanced after administration of Spirulina in >50% subjects. IFN gamma was produced in an IL-12/IL-18-dependent fashion. In vitro stimulation of blood cells with BCG cell wall skeleton (CWS) allowed more potent IL-12 p40 production in cells from volunteers given Spirulina than in cells without pre-exposure to Spirulina. As BCG-CWS serves as a ligand for Toll-like receptor (TLR) 2 and 4 to raise the maturation stage of monocytes/macrophages, Spirulina may be involved in the signaling responses through Toll in blood cells even when orally administered. These observations indicated that in humans Spirulina acts directly on myeloid lineages and either directly or indirectly on NK cells. The presence of co-operative IL-12 and IL-18 is critically important for NK-mediated IFN gamma production.
Subchronic toxicity study in mice fed Spirulina maxima A sensitive assay system screening antiviral compounds against herpes simplex virus type 1 and type 2
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