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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.


Lactoferrin SARS-CoV-2 COVID-19 Immunomodulation Antiviral

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How to Cite
Azhar, J. ., Mohammadabadi, T. ., Babar, M. E. ., & Hussain, T. . (2020). Milk Lactoferrin: A Probable Immunological Agent Against SARS-CoV-2 : A Review. Basrah Journal of Agricultural Sciences, 33(2), 138–146.


  1. 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.
  2. 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.
  3. Anghel, L. (2014). Lactoferrin: analysis of the structure profile. Chemistry Journal of Moldova, 9, 99-106.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Chen, Y., Liu, Q., & Guo, D. (2020). Emerging coronaviruses: genome structure, replication, and pathogenesis. Journal of Medical Virology, 92, 418-423.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Gonzalez-Chavez, S.A., Arevalo-Gallegos, S., & Rascon-Cruz, Q. (2009). Lactoferrin: structure, function and applications. International Journal of Antimicrobial Agents, 33, 301-308.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. Jenssen, H., & Hancock. R. E. W. (2009). Antimicrobial properties of lactoferrin. Biochimie, 91, 19-29.
  21. 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.
  22. Kuchler, H., Cookson, C., & Neville, S. (2020). The $2 bn race to find a vaccine. Financial Times, 7.
  23. 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.
  24. 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.
  25. Legrand, D. (2012). Lactoferrin, a key molecule in immune and inflammatory processes. Biochemistry and Cell Biology, 90, 252–268.
  26. Legrand, D., & Mazurier, J. (2010). A critical review of the roles of host lactoferrin in immunity. Biometals, 23, 365-376.
  27. Lepanto, M. S., Rosa, L., Paesano, R., Valenti, P., & Cutone, A. (2019). Lactoferrin in aseptic and septic inflammation. Molecules, 24, 1323.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. Orsi, N. (2004). The antimicrobial activity of lactoferrin: Current status and perspectives. Biometals, 17, 189-196.
  35. Puddu, P., Valenti, P., & Gessani, S. (2009). Immunomodulatory effects of lactoferrin on antigen presenting cells. Biochimie, 91, 11-18.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. 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.
  41. Sorensen, M., & Sorensen, S. (1939). Compte rendu des Travaux du Laboratoire de Carlsberg. The Proteins in Whey, 83, 432., 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.
  42. 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.
  43. Suzuki, Y. A., Lopez, V., & Lönnerdal, B. (2005). Lactoferrin. Cellular and Molecular Life Sciences, 62, 2560.
  44. 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.
  45. Valenti, P., & Antonini, G. (2005). Lactoferrin: an important host defence against microbial and viral attack. Cellular and Molecular Life Sciences, 62, 2576-2587.
  46. 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.
  47. Wu, D., Lewis, E. D., Pae, M., & Meydani, S. N. (2019). Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Frontiers in Immunology, 9, 3160.
  48. Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., & Niu, P. (2020). A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine, 382, 727-733.