Table 1.
Summary of antiviral studies with lactoferrin. In silico, in vitro, and clinical trials utilizing human, bovine, or other sources of lactoferrin are outlined below with the source of lactoferrin, route of administration (if in vivo), and summary of the relevant results from the main text.
| Author (Year) [Citation] | Model | Lactoferrin Source Route (Dose) |
Brief Results |
|---|---|---|---|
| Sinopoli et al. (2022) [6] | Systemic Review |
NA | Systemic review of clinical trials using orally administered Lf for the treatment of viral infections. |
| Marchetti et al. (1996) [42] | Primate In vitro |
hLf bLf |
Lf inhibits HSV1 absorption with bLf showing better efficacy than hLf. |
| Lu et al. (1987) [39] | Murine In vivo |
hLf i.p. |
hLf shown to have protective effects against the polycythemia-inducing strain of the friend virus complex in mice. |
| Marchetti et al. (1998) [43] | Primate In vitro |
bLf | The antiviral activity of Lf appears to correlate with the degree of its metal binding and saturation. |
| Yi et al. (1997) [44] | In vitro | bLf hLf |
Demonstrates interaction of Lf and HCV envelope proteins. |
| Marchetti et al. (1999) [45] | Primate In vitro |
bLf | Suggests bLf plays a role in altering viral infection, particularly in the gut, through the inhibition of certain steps of viral infection. |
| Superti et al. (2001) [46] | Primate In vitro |
bLf | bLf inhibits rotavirus through a different mechanism than the previously reported for HPV. |
| El-Fakharany (2013) [47] | Human In vitro |
hLf bLf camel Lf sheep Lf |
Human, camel, bovine, and sheep Lf prevent HCV entry into cells by binding the virus; camel Lf was most effective. |
| Hara et al. (2002) [48] | Human In vitro |
bLf hLf |
Lf inhibits HBV infection in vitro. |
| Ishii et al. (2003) [49] | Human Clinical |
bLf oral (0.6 g/day) |
Increased IL-18 with oral bLf supplement in chronic HCV patients. |
| Okada et al. (2002) [40] | Human Clinical |
bLf oral (1.8–7.2 g/day) |
bLf use in chronic hepatitis C patients is well tolerated. |
| El-Ansary et al. (2016) [50] | Human Clinical |
bLf oral (0.5 g/day) |
Increased CD4, CD8, CD137, and CD56 levels with bLf supplementation in chronic HCV patients |
| Ueno et al. (2006) [41] | Humans Clinical |
bLf oral (1.8 g/day) |
Oral Lf has a negligible impact on viral load when taken orally by patients with chronic HCV. |
| Tanaka et al. (1999) [51] | Humans Clinical |
bLf oral (1.8–6 g/day) |
Lf could be used as an anti-HCV adjuvant therapy with the potential to help treat chronic hepatitis. |
| Hirashima et al. (2004) [52] | Human Clinical |
bLf oral (9.0 g/day) |
Lf did not increase the response rate or prevent relapse after discontinuing interferon in chronic HCV patients. |
| Ishibashi et al. (2005) [53] | Human Clinical |
bLf oral (0.6 g/day) |
This study failed to demonstrate that Lf in combination with antiviral therapy provided additional benefit to chronic HCV patients. |
| Kaito et al. (2007) [54] | Human Clinical |
bLF oral (3.6 g/day) |
Lf was shown to increase the effectiveness of interferon and ribavirin therapy in chronic HCV patients. |
| Konishi et al. (2006) [55] | Human Clinical |
bLf oral (3.6 g/day) |
Decreased ALT levels and plasma 8-isoprostane in chronic HCV patients. |
| Ochoa et al. (2013) [56] | Human Clinical |
bLf oral (0.5 g/day) |
Decreased duration and symptoms in norovirus patients. |
| Egashira et al. (2007) [57] | Human Clinical |
bLf oral (100 mg/day) |
Decreased frequency and duration of symptoms in rotavirus patients. |
| Zuccotti et al. (2007) [58] | Human Clinical |
bLf oral (3 g/day) |
Observed decline in viral load during bLf administration in HIV patients. |
| Mirabelli et al. (2020) [59] | Human Primate In vitro |
bLf hLf |
Lf effective, in vitro, at inhibiting COVID through multiple mechanisms. |
| Salaris et al. (2021) [60] | Human Primate In vitro |
bLf | Lf-moderated immunity during SARS-CoV-2 infection. |
| Oda et al. (2021) [61] | Human In vitro |
bLF | bLf demonstrates antiviral activity against the human norovirus |
| Wotring et al. (2022) [62] | Human In vitro |
bLf | Dairy product efficacy in inhibiting SARS-CoV-2 infection was dependent on Lf concentration; bLf retained efficacy against SARS-CoV-2 viral variants of concern. |
| Miotto et al. (2021) [63] | In silico | hLF | Computational modeling indicated that Lf blocks SARS-CoV-2 infection through competitive binding with the spike protein. |
| Piacentini et al. (2022) [64] | In silico | hLf | Lf binds to ACE2 receptor and not SARS-CoV-2 spike protein RBD. |
| Campione et al. (2021) [65] | Human Primate In vitro |
bLf | Lf effective antiviral against SARS-CoV-2 infection in vitro. |
| Cutone et al. (2022) [66] | Human In vitro |
bLf | Preincubation with bLf inhibited SARS-CoV-2 binding and pseudovirus entry into epithelial and macrophage-like cells, reduced inflammatory response, and increased gene expression associated with iron homeostasis. |
| Serrano et al. (2020) [67] | Human Clinical |
bLf oral (20–30 mg/day) |
Improvement in reported symptoms in mild to moderate COVID-19 patients. |
| Campione et al. (2020) [68] | Human Clinical |
bLf oral (1 g/day) |
Decreased time to negative molecular test and duration of symptoms in COVID-19 patients |
| Algahtani et al. (2021) [69] | Human Clinical |
bLf oral (200–400 mg/day) |
No statistical difference between treatment and non-treatment groups, but trends in symptom improvement and blood biomarker profile observed. |
| Rosa et al. (2021) [70] | Human Clinical |
bLf oral (200–1000 mg/day) |
Reduced time to negative molecular SARS-CoV-2 test, reported reduction in symptoms of COVID-19 patients of advanced age. |
Abbreviations: NA = Not applicable, bLf = bovine lactoferrin, hLf = human lactoferrin, i.p. = intraperitoneal.