Well-tolerated spirulina extract inhibits influenza virus replication and reduces virus-induced mortality
Open accessAbstract
Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts and specific substances derived from Spirulina, and here we show that this Spirulina cold water extract has low cellular toxicity, and is well-tolerated in animal models at one dose as high as 5,000 mg/kg, or 3,000 mg/kg/day for 14 successive days. Anti-flu efficacy studies revealed that the Spirulina extract inhibited viral plaque formation in a broad range of influenza viruses, including oseltamivir-resistant strains. Spirulina extract was found to act at an early stage of infection to reduce virus yields in cells and improve survival in influenza-infected mice, with inhibition of influenza hemagglutination identified as one of the mechanisms involved. Together, these results suggest that the cold water extract of Spirulina might serve as a safe and effective therapeutic agent to manage influenza outbreaks, and further clinical investigation may be warranted.
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Spirulina has shown antiviral activities against certain common human or animal viruses.
“Additionally, Spirulina has shown antiviral activities against certain common human or animal viruses and this capability can be considered to exhibit potential benefits against avian viruses also.”
From Potential of Spirulina platensis as a feed supplement for poultry to enhance growth performance and immune modulation (2023) · cites this paper as [58]
Spirulina use as a feed additive faces challenges of higher cost compared to other protein ingredients, limited large-scale production, and sustainability issues.
“Another major challenge regarding use of Spirulina as a feed addtitve is its quite higher cost compared to other protein ingredients such as soybean meal (58, 86).”
From Potential of Spirulina platensis as a feed supplement for poultry to enhance growth performance and immune modulation (2023) · cites this paper as [58]
The Discussion addresses chemical characterization and quality control of a Spirulina extract for clinical trials, not its cost as a feed additive. Searches for a soybean-meal cost comparison and for large-scale production and sustainability found no passages addressing those claims in our copy. (LLM, conf=0.76)
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Cites
Updating the accounts: global mortality of the 1918–1920 "Spanish" influenza pandemic.
Johnson, N. P. A. S., & Mueller, J. (2002) · Bulletin of the History of Medicine · doi:10.1353/bhm.2002.0022 · Cited by 1,980 · see citing works
Emergence and pandemic potential of swine-origin H1N1 influenza virus
Neumann, G., Noda, T., & Kawaoka, Y. (2009) · Nature · doi:10.1038/nature08157 · Cited by 1,562 · see citing works
New World Bats Harbor Diverse Influenza A Viruses
Tong, S., Zhu, X., Li, Y., Shī, M., Zhang, J., Bourgeois, M. A., Yang, H., Chen, X., Recuenco, S., Gómez, J., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003657 · Cited by 1,353 · see citing works
Dawood, F. S., Iuliano, A., Reed, C., Meltzer, M., Shay, D., Cheng, P.-Y., Bandaranayake, D., Breiman, R., Brooks, W. A., Buchy, P., et al. (2012) · Lancet. Infectious Diseases (Print) · doi:10.1016/s1473-3099(12)70121-4 · Cited by 1,294 · see citing works
The Pathology of Influenza Virus Infections
Taubenberger, J. K., & Morens, D. M. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.154316 · Cited by 1,111 · see citing works
Pandemic Preparedness and Response — Lessons from the H1N1 Influenza of 2009
Fineberg, H. V. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1208802 · Cited by 562 · see citing works
Global Influenza Seasonality: Reconciling Patterns across Temperate and Tropical Regions
Tamerius, J. D., Nelson, M. I., Zhou, S., Viboud, C. G., Miller, M. A., & Alonso, W. J. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.1002383 · Cited by 519 · see citing works
Jefferson, T., Jones, M., Doshi, P., Spencer, E. A., Onakpoya, I., & Heneghan, C. J. (2014) · BMJ · doi:10.1136/bmj.g2545 · Cited by 449 · see citing works
Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae <i>Spirulina</i>
Deng, R., & Chow, T. (2010) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2010.00200.x · Cited by 435 · see citing works
Hayashi, T., Hayashi, K., Maeda, M., & Kojima, I. (1996) · Journal of Natural Products · doi:10.1021/np960017o · Cited by 422 · see citing works
Spirulina in Clinical Practice: Evidence‐Based Human Applications
Karkos, P. D., Leong, S. C., Karkos, C. D., Sivaji, N., & Assimakopoulos, D. A. (2008) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/nen058 · Cited by 332 · see citing works
Hayashi (1996) · doi:10.1089/aid.1996.12.1463 · Cited by 320 · see citing works
Selective inhibition of cyclooxygenase-2 by C-phycocyanin, a biliprotein from Spirulina platensis
Reddy, C. M., Bhat, V. B., Kiranmai, G., Reddy, M. N., Reddanna, P., & Madyastha, K. M. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3725 · Cited by 310 · see citing works
Zheng, B.-J., Chan, K.-W., Lin, Y.-P., Zhao, G.-Y., Chan, C., Zhang, H.-J., Chen, H.-L., Wong, S. S. Y., Lau, S. K. P., Woo, P. C. Y., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711942105 · Cited by 302 · see citing works
Hirahashi, T., Matsumoto, M., Hazeki, K., Saeki, Y., Ui, M., & Seya, T. (2002) · International Immunopharmacology · doi:10.1016/s1567-5769(01)00166-7 · Cited by 288 · see citing works
Geiler, J., Michaelis, M., Naczk, P., Leutz, A., Langer, K., Doerr, H.-W., & Cinatl, J. J. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.08.025 · Cited by 205 · see citing works
Antivirals and resistance: influenza virus
Ison, M. G. (2011) · Current Opinion in Virology · doi:10.1016/j.coviro.2011.09.002 · Cited by 193 · see citing works
Inhibition of HIV-1 Replication by an Aqueous Extract of Spirulina platensis (Arthrospira platensis)
Ayehunie, S., Belay, A., Baba, T. W., & Ruprecht, R. M. (1998) · Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology · doi:10.1097/00042560-199805010-00002 · Cited by 186 · see citing works
Mao, T. K., Water, J. V. D., & Gershwin, M. E. (2005) · Journal of Medicinal Food · doi:10.1089/jmf.2005.8.27 · Cited by 185 · see citing works
United States Pharmacopeia Safety Evaluation of Spirulina
Marles, R. J., Barrett, M. L., Barnes, J., Chavez, M. L., Gardiner, P., Ko, R., Mahady, G. B., Dog, T. L., Sarma, N. D., Giancaspro, G. I., et al. (2011) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408391003721719 · Cited by 177 · see citing works
Shih, S., Tsai, K., Li, Y., Chueh, C., & Chan, E. (2003) · Journal of Medical Virology · doi:10.1002/jmv.10363 · Cited by 145 · see citing works
Self-citationAntiinflammatory and Antihyperalgesic Activity of C-Phycocyanin
Shih, C.-M., Cheng, S., Wong, C., Kuo, Y.-L., & Chou, T. (2009) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e318193e919 · Cited by 143 · see citing works
Anti-inflammatory activity of c-phycocyanin in lipopolysaccharide-stimulated RAW 264.7 macrophages
Cherng, S.-C., Cheng, S.-N., Tarn, A., & Chou, T.-C. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.09.009 · Cited by 136 · see citing works
Lee, S. M. Y., Cheung, C. Y., Nicholls, J. M., Hui, K. P. Y., Leung, C. Y. H., Uiprasertkul, M., Tipoe, G. L., Lau, Y., Poon, L. L. M., Ip, N. Y., et al. (2008) · The Journal of Infectious Diseases · doi:10.1086/590499 · Cited by 122 · see citing works
Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity
Shih, S., Chu, T. Y., Reddy, G. R., et al. (2010) · Journal of Biomedical Science · doi:10.1186/1423-0127-17-13 · Cited by 111 · see citing works
Self-citationThe effects of spirulina on allergic rhinitis
Cingi, C., Conk-Dalay, M., Cakli, H., & Bal, C. (2008) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-008-0642-8 · Cited by 98 · see citing works
Hayashi, K., Hayashi, T., Morita, N., & Kojima, I. (1993) · Phytotherapy Research · doi:10.1002/ptr.2650070118 · Cited by 89 · see citing works
Hwang, J.-H., Chen, J.-C., & Chan, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058215 · Cited by 80 · see citing works
Simpore, J., Zongo, F., Kabore, F., Dansou, D., Bere, A., Nikiema, J.-B., Pignatelli, S., Biondi, D. M., Ruberto, G., & Musumeci, S. (2005) · Annals of Nutrition and Metabolism · doi:10.1159/000088889 · Cited by 80 · see citing works
Lee, J., Preeprame, S., Hayashi, K., TANAKA, T., Sankawa, U., & Hayashi, T. (2001) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.49.108 · Cited by 75 · see citing works
Leung, P., Lee, H., Kung, Y.-C., Tsai, M.-F., & Chou, T. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/916590 · Cited by 59 · see citing works
Pugh, N. D., Edwall, D., Lindmark, L., Kousoulas, K. G., Iyer, A. V., Haron, M. H., & Pasco, D. S. (2014) · Phytomedicine · doi:10.1016/j.phymed.2014.12.006 · Cited by 35 · see citing works
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Abd El-Hack, M. E., Abdelnour, S., Alagawany, M., Abdo, M., Sakr, M. A., Khafaga, A. F., Mahgoub, S. A., Elnesr, S. S., & Gebriel, M. G. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.12.069 · Cited by 206 · see citing works
Spínola, M. P., Mendes, A. R., & Prates, J. A. M. (2024) · Foods · doi:10.3390/foods13223656 · Cited by 146 · see citing works
Ma, H., Xiong, H., Zhu, X., Ji, C., Xue, J., Li, R., Ge, B., & Cui, H. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.04.209 · Cited by 100 · see citing works
El-Shall, N. A., Jiang, S., Farag, M. R., Azzam, M., Al-Abdullatif, A. A., Alhotan, R., Dhama, K., Hassan, F.-U., & Alagawany, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1072787 · Cited by 115 · see citing works
“Second major challenge with spirulina is limitation of its large scale production as presently it is produced at a smaller scale primarily for the nutritional supplement sector with few exceptions (58).”
BackgroundAnti-Oxidation Properties and Therapeutic Potentials of Spirulina
Han, P., Li, J., Zhong, H., Xie, J., Zhang, P., Lu, Q., Li, J., Xu, P., Chen, P., Leng, L., et al. (2021) · Algal Research · doi:10.1016/j.algal.2021.102240 · Cited by 109 · see citing works
Pentón-Rol, G., Marín-Prida, J., & McCarty, M. F. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210408123807 · Cited by 73 · see citing works
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Mazur-Marzec, H., Cegłowska, M., Konkel, R., & Pyrć, K. (2021) · Biomolecules · doi:10.3390/biom11030474 · Cited by 64 · see citing works
Tzachor, A., Smidt-Jensen, A., Ramel, A., & Geirsdóttir, M. (2022) · Marine Biotechnology · doi:10.1007/s10126-022-10162-8 · Cited by 52 · see citing works
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Dehghani, J., Adibkia, K., Movafeghi, A., Barzegari, A., Pourseif, M. M., Maleki Kakelar, H., Golchin, A., & Omidi, Y. (2018) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-018-9296-7 · Cited by 43 · see citing works
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- Authors
- Chen, Y.-H., Chang, G.-K., Kuo, S.-M., Huang, S.-Y., Hu, I.-C., Lo, Y.-L., & Shih, S.-R.
- Affiliations
- Chang Gung University (TW)
- National Tsing Hua University (TW)
- Corresponding author
- Shih, Shin-Ru
- Venue
- Scientific Reports
- Published
- 2016-04-12
- Volume
- 6
- Issue
- 1
- Pages
- 24253-24253
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4828654
- OpenAlex
- W2337925055
- Cited by
- 112
- References
- 32
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 18 · 2023: 10 · 2022: 22 · 2021: 18 · 2020: 15 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 1
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Chang Gung University
- Chang Gung Medical Foundation
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
- Keywords
- Spirulina, Spirulina platensis, influenza virus, antiviral activity, cold water extract, oseltamivir resistance, hemagglutination inhibition, toxicity, natural products
- MeSH terms
- Animals, Antiviral Agents, Cell Survival, Dogs, Orthomyxoviridae, Orthomyxoviridae Infections, Viral Plaque Assay, Virus Replication, Survival Analysis, Treatment Outcome, Mice, Spirulina, Madin Darby Canine Kidney Cells
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