Main Article Content
Abstract
In current COVID-19 pandemic, when there is no specific antiviral treatment and vaccine is available yet, many nutritional supplements have caught the attention to manage the disease. Lactoferrin is one of a natural nutritional supplement found in the milk of livestock mammals and has immunomodulation property due to its iron withholding ability and capacity to bind to multiple cellular receptors. The antiviral ability of lactoferrin has been evaluated against many viruses including SARS-CoV which is closely related to SARS-CoV-2 (causative agent of COVID-19). Furthermore, lactoferrin also possesses anti-inflammatory efficacy and can inhibit the circulating inflammatory cytokines (e.g. Interferon γ, interleukin (IL-) 1B, IL-6, IL-12) and chemokines (CCL2 and CXCL10) which are reported to be present in higher levels in COVID-19 patients. A particular research about exploring the potential of lactoferrin against SARS-CoV-2 is highly demandable because lactoferrin might prevent the SARS-CoV-2 from infecting the host cells due to its biological activities regarding antiviral immunity. We are hopeful that further research on evaluating the pharmacological effect of lactoferrin against SARS-CoV-2 will signify its role to combat COVID-19.
Keywords
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References
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- Ishii, K, Takamura, N., & Shinohara, M. (2003). Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months. Hepatology Research, 25, 226e33. https://doi.org/10.1016/s1386-6346(02)00279-6
- Jayawardena, R., Sooriyaarachchi, P., Chourdakis, M., Jeewandara, C., & Ranasinghe, P. (2020). Enhancing immunity in viral infections, with special emphasis on COVID-19: A review. Diabetes & Metabolic Syndrome, 14, 367–382. https://doi.org/10.1016/j.dsx.2020.04.015.
- Jenssen, H., & Hancock. R. E. W. (2009). Antimicrobial properties of lactoferrin. Biochimie, 91, 19-29. https://doi.org/10.1016/j.biochi.2008.05.015
- Kell, D. B., Heyden, E. L., & Pretorius, E. (2020). The Biology of Lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. Frontiers in Immunology, 11, 1221. https://doi.org/10.3389/fimmu.2020.01221
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- Legrand, D., Elass, E., Carpentier, M., & Mazurier, J. (2006). Interactions of lactoferrin with cells involved in immune function. Biochemistry and Cell Biology, 84: 282-290. https://doi.org/10.1139/o06-045
- Legrand, D. (2012). Lactoferrin, a key molecule in immune and inflammatory processes. Biochemistry and Cell Biology, 90, 252–268. https://www.nrcresearchpress.com/doi/abs/10.1139/o11-056
- Legrand, D., & Mazurier, J. (2010). A critical review of the roles of host lactoferrin in immunity. Biometals, 23, 365-376. https://doi.org/10.1007/s10534-010-9297-1
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- Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020). Across Specialty Collaboration, U. COVID-19: Consider cytokine storm syndromes and immunosuppression. The Lancet, 395, 1033-1034.https://doi.org/10.1016/s0140-6736(20)30628-0
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- Okubo, K., Kamiya, M., Urano, Y., Nishi, H., Herter, J. M., Mayadas, T., & Kurosawa, M. (2016). Lactoferrin suppresses neutrophil extracellular traps release in inflammation. E BioMedicine, 10, 204-215. https://doi.org/10.1016/j.ebiom.2016.07.012
- Orsi, N. (2004). The antimicrobial activity of lactoferrin: Current status and perspectives. Biometals, 17, 189-196. https://doi.org/10.1023/b:biom.0000027691.86757.e2
- Puddu, P., Valenti, P., & Gessani, S. (2009). Immunomodulatory effects of lactoferrin on antigen presenting cells. Biochimie, 91, 11-18. https://doi.org/10.1016/j.biochi.2008.05.005
- Perdijk, O., van Splunter, M., Savelkoul, H. F., Brugman, S., & van Neerven, R. J. (2018). Cow’s milk and immune function in the respiratory tract: Potential mechanisms. Frontiers in Immunology, 9, 143. https://doi.org/10.3389/fimmu.2018.00143
- Queiroz, V. A. O., Assis, A. M. O., & Júnior, H. C. R. (2013). Protective effect of human lactoferrin in the gastrointestinal tract. Revista Paulista de Pediatria, 31, 90-95. https://doi.org/10.1590/s0103-05822013000100015
- Rawat, P., Kumar, S., Sheokand, N., Raje, C. I., & Raje, M. (2012). The multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a novel macrophage lactoferrin receptor. Biochemistry and Cell Biology, 90, 329-338. https://doi.org/10.1139/o11-058
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- Suzuki, Y. A., Lopez, V., & Lönnerdal, B. (2005). Lactoferrin. Cellular and Molecular Life Sciences, 62, 2560. https://doi.org/10.1007/s00018-005-5371-1
- Takayama, Y., Aoki, R., Uchida, R., Tajima, A., & Aoki-Yoshida, A. (2017). Role of CXC chemokine receptor type 4 as a lactoferrin receptor. Biochemistry and Cell Biology, 95, 57-63. https://doi.org/10.1139/bcb-2016-0039
- Valenti, P., & Antonini, G. (2005). Lactoferrin: an important host defence against microbial and viral attack. Cellular and Molecular Life Sciences, 62, 2576-2587. https://doi.org/10.1007/s00018-005-5372-0
- Van der Strate, W. A., Beljaars, L., Molema, G., Harmsen, M. C., & Meijer D. K. F. (2001). Antiviral activities of lactoferrin. Antiviral Research, 52, 225–239. https://doi.org/10.1016/s0166-3542(01)00195-4
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References
Al-Hatim, R. R., Al-Rikabi, A. K., & Ghadban, A. K. (2020). The Physico-chemical properties of bovine and buffalo whey proteins milk by using ultrafiltration membrane Technology. Basrah Journal of Agricultural Sciences, 33, 122-134. https://doi.org/10.37077/25200860.2020.33.1.10
Al-Majali, A. M., Ismail, Z. B., Al-Hami, Y., & Nour, A. Y. (2007). Lactoferrin concentration in milk from camels (Camelus dromedarius) with and without subclinical mastitis. International Journal of Applied Research in Veterinary Medicine, 5, 120. http://jarvm.com/articles/Vol5Iss3/
Anghel, L. (2014). Lactoferrin: analysis of the structure profile. Chemistry Journal of Moldova, 9, 99-106. https://doi.org/10.19261/cjm.2014.09(2).14.
Berlutti, F., Pantanella, F., Natalizi, T., Frioni, A., Paesano, R., Polimeni, A., & Valenti, P. (2011). Antiviral properties of lactoferrin- A natural immunity molecule. Molecules, 16, 6992-7018. https://doi.org/10.3390/molecules16086992.
Britigan, B. E., Lewis, T. S., Waldschmidt, M., McCormick, M. L., & Krieg, A. M. (2001). Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. The Journal of Immunology, 167, 2921-2928. https://doi.org/10.4049/jimmunol.167.5.2921
Bruni, N., Capucchio, M. T., Biasibetti, E., Pessione, E., Cirrincione, S., Giraudo, L., Corona, A., & Dosio, F. (2016). Antimicrobial activity of lactoferrin-related peptides and applications in human and veterinary medicine. Molecules (Basel, Switzerland), 21. https://doi.org/10.3390/molecules21060752
Cheng, J. B., Wang, J. Q., Bu, D. P., Liu, G. L., Zhang, C. G., Wei, H. Y., Zhou, L. Y., & Wang, J. Z. (2008). Factors affecting the lactoferrin concentration in bovine milk. Journal of Dairy Science, 91, 970-976. https://doi.org/10.3168/jds.2007-0689
Chen, Y., Liu, Q., & Guo, D. (2020). Emerging coronaviruses: genome structure, replication, and pathogenesis. Journal of Medical Virology, 92, 418-423. https://doi.org/10.1002/jmv.25681
Claeys, W. L., Cardoen, S., Daube, G., De Block, J., Dewettinck, K., Dierick, K., & Vandenplas, Y. (2013). Raw or heated cow milk consumption: Review of risks and benefits. Food Control, 31, 251-262. https://doi.org/10.1016/j.foodcont.2012.09.035
Conesa, C., Sánchez, L., Rota, C., Pérez, M. D., Calvo, M., Farnaud, S., & Evans, R. W. (2008). Isolation of lactoferrin from milk of different species: calorimetric and antimicrobial studies. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 150, 131-139. https://doi.org/10.1016/j.cbpb.2008.02.005
El-Hatmi, H., Girardet, J., Gaillard, J., Yahyaoui, M. H., & Attia, H. (2007). Characterization of whey proteins of camel (Camelus dromedarius) milk and colostrum. Small Ruminant Research, 70, 267-271. https://doi.org/10.1016/j.smallrumres.2006.04.001
Embleton, N., D., Berrington, J. E., Chris, W. M., & Cummings, S. S. (2013). Lactoferrin: Antimicrobial activity and therapeutic potential. Seminars in Fetal & Neonatal Medicine, 18, 143-149. https://doi.org/10.1016/j.siny.2013.02.001
Furmanski, P., Li, Z. P., Fortuna, M. B., Swamy, C. V., & Das, M. R. (1989). Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity. Journal of Experimental Medicine, 170, 415-429. https://doi.org/10.1084/jem.170.2.415
Gao, C. H., Dong, H. L., Tai, L., & Gao, X. M. (2018). Lactoferrin-containing immunocomplexes drive the conversion of human macrophages from M2-into M1-like phenotype. Frontiers in Immunology, 9, 37. https://doi.org/10.3389/fimmu.2018.00037
Gonzalez-Chavez, S.A., Arevalo-Gallegos, S., & Rascon-Cruz, Q. (2009). Lactoferrin: structure, function and applications. International Journal of Antimicrobial Agents, 33, 301-308. https://doi.org/10.1016/j.ijantimicag.2008.07.020
Gombart, A. F., Pierre, A., & Maggini, S. (2020). A Review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients, 12, 236. https://doi.org/10.3390/nu12010236
Iglesias-Figueroa, B. F., Espinoza-Sánchez, E. A., Siqueiros-Cendón, T. S., & Rascón-Cruz, Q. (2019). Lactoferrin as a nutraceutical protein from milk, an overview. International Dairy Journal, 89, 37-41. https://doi.org/10.1016/j.idairyj.2018.09.004
Ishii, K, Takamura, N., & Shinohara, M. (2003). Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months. Hepatology Research, 25, 226e33. https://doi.org/10.1016/s1386-6346(02)00279-6
Jayawardena, R., Sooriyaarachchi, P., Chourdakis, M., Jeewandara, C., & Ranasinghe, P. (2020). Enhancing immunity in viral infections, with special emphasis on COVID-19: A review. Diabetes & Metabolic Syndrome, 14, 367–382. https://doi.org/10.1016/j.dsx.2020.04.015.
Jenssen, H., & Hancock. R. E. W. (2009). Antimicrobial properties of lactoferrin. Biochimie, 91, 19-29. https://doi.org/10.1016/j.biochi.2008.05.015
Kell, D. B., Heyden, E. L., & Pretorius, E. (2020). The Biology of Lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. Frontiers in Immunology, 11, 1221. https://doi.org/10.3389/fimmu.2020.01221
Kuchler, H., Cookson, C., & Neville, S. (2020). The $2 bn race to find a vaccine. Financial Times, 7. https://www.ft.com/content/e0ecc6b6-5d43-11ea-b0ab-339c2307bcd4
Lang, J., Yang, N., Deng, J., Liu, K., Yang, P., Zhang, G., & Jiang, C. (2011). Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PLoS one, 6 e23710. https://doi.org/10.1371/journal.pone.0023710
Legrand, D., Elass, E., Carpentier, M., & Mazurier, J. (2006). Interactions of lactoferrin with cells involved in immune function. Biochemistry and Cell Biology, 84: 282-290. https://doi.org/10.1139/o06-045
Legrand, D. (2012). Lactoferrin, a key molecule in immune and inflammatory processes. Biochemistry and Cell Biology, 90, 252–268. https://www.nrcresearchpress.com/doi/abs/10.1139/o11-056
Legrand, D., & Mazurier, J. (2010). A critical review of the roles of host lactoferrin in immunity. Biometals, 23, 365-376. https://doi.org/10.1007/s10534-010-9297-1
Lepanto, M. S., Rosa, L., Paesano, R., Valenti, P., & Cutone, A. (2019). Lactoferrin in aseptic and septic inflammation. Molecules, 24, 1323. https://doi.org/10.3390/molecules24071323
Liao, Y., Jiang, R., & Lönnerdal, B. (2012). Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life. Biochemistry and Cell Biology, 90, 476-484. https://doi.org/10.1139/o11-075
Loss, G., Depner, M., Ulfman, L. H., Van Neerven, R. J., Hose, A. J., Genuneit, J., & Weber, J. (2015). Consumption of unprocessed cow's milk protects infants from common respiratory infections. Journal of Allergy and Clinical Immunology, 135, 56-62. https://doi.org/10.1016/j.jaci.2014.08.044
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020). Across Specialty Collaboration, U. COVID-19: Consider cytokine storm syndromes and immunosuppression. The Lancet, 395, 1033-1034.https://doi.org/10.1016/s0140-6736(20)30628-0
Milewska, A., Zarebski, M., Nowak, P., Stozek, K., Potempa, J., & Pyrc, K. (2014). Human coronavirus NL63 utilizes heparan sulfate proteoglycans for attachment to target cells. Journal of Virology, 88, 13221-13230. https://doi.org/10.1128/jvi.02078-14
Moore, S. A., Anderson, B. F., Groom, C. R., Haridas, M., & Baker, E. N. (1997). Three-dimensional structure of diferric bovine lactoferrin at 2.8 Å resolution. Journal of Molecular Biology, 274, 222-236. https://doi.org/10.2210/pdb1blf/pdb
Okubo, K., Kamiya, M., Urano, Y., Nishi, H., Herter, J. M., Mayadas, T., & Kurosawa, M. (2016). Lactoferrin suppresses neutrophil extracellular traps release in inflammation. E BioMedicine, 10, 204-215. https://doi.org/10.1016/j.ebiom.2016.07.012
Orsi, N. (2004). The antimicrobial activity of lactoferrin: Current status and perspectives. Biometals, 17, 189-196. https://doi.org/10.1023/b:biom.0000027691.86757.e2
Puddu, P., Valenti, P., & Gessani, S. (2009). Immunomodulatory effects of lactoferrin on antigen presenting cells. Biochimie, 91, 11-18. https://doi.org/10.1016/j.biochi.2008.05.005
Perdijk, O., van Splunter, M., Savelkoul, H. F., Brugman, S., & van Neerven, R. J. (2018). Cow’s milk and immune function in the respiratory tract: Potential mechanisms. Frontiers in Immunology, 9, 143. https://doi.org/10.3389/fimmu.2018.00143
Queiroz, V. A. O., Assis, A. M. O., & Júnior, H. C. R. (2013). Protective effect of human lactoferrin in the gastrointestinal tract. Revista Paulista de Pediatria, 31, 90-95. https://doi.org/10.1590/s0103-05822013000100015
Rawat, P., Kumar, S., Sheokand, N., Raje, C. I., & Raje, M. (2012). The multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a novel macrophage lactoferrin receptor. Biochemistry and Cell Biology, 90, 329-338. https://doi.org/10.1139/o11-058
Shereen, M. A., Khan, S., Kazmi, A., Bashir, N., & Siddique, R. (2020). COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. Journal of Advanced Research, 94, 91-98. https://doi.org/10.1016/j.jare.2020.03.005
Shin, K., Wakabayashi, H., Yamauchi, K., Yaeshima, T., & Iwatsuki, K. (2008). Recombinant human intelectin binds bovine lactoferrin and its peptides. Biological and Pharmaceutical Bulletin, 31, 1605-1608. https://doi.org/10.1248/bpb.31.1605
Sorensen, M., & Sorensen, S. (1939). Compte rendu des Travaux du Laboratoire de Carlsberg. The Proteins in Whey, 83, 432. https://doi.org/10.3406/crai.1939.85865.Stelwagen, K., Carpenter, E., Haigh, B., Hodgkinson, A., & Wheeler, T. T. (2009). Immune components of bovine colostrum and milk. Journal of Animal Science, 87, 3-9. https://doi.org/10.2527/jas.2008-1377
Superti, F., Berlutti, F., Paesano, R., & Valenti, P. (2008). Structure and activity of lactoferrin -A multi-functional protective agent for human health. 1-32. In Fuchs, H., (Ed.). Iron Metabolism and Disease; Research Signpost: Kerala.
Suzuki, Y. A., Lopez, V., & Lönnerdal, B. (2005). Lactoferrin. Cellular and Molecular Life Sciences, 62, 2560. https://doi.org/10.1007/s00018-005-5371-1
Takayama, Y., Aoki, R., Uchida, R., Tajima, A., & Aoki-Yoshida, A. (2017). Role of CXC chemokine receptor type 4 as a lactoferrin receptor. Biochemistry and Cell Biology, 95, 57-63. https://doi.org/10.1139/bcb-2016-0039
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