An overview on in vitro and in vivo antiviral activity of lactoferrin: its efficacy against SARS-CoV-2 infection

Abstract

Beyond the absolute and indisputable relevance and efficacy of anti-SARS-CoV-2 vaccines, the rapid transmission, the severity of infection, the absence of the protection on immunocompromised patients, the propagation of variants, the onset of infection and/or disease in vaccinated subjects and the lack of availability of worldwide vaccination require additional antiviral treatments. Since 1987, lactoferrin (Lf) is well-known to possess an antiviral activity related to its physico-chemical properties and to its ability to bind to both heparan sulfate proteoglycans (HSPGs) of host cells and/or surface components of viral particles. In the present review, we summarize in vitro and in vivo studies concerning the efficacy of Lf against DNA, RNA, enveloped and non-enveloped viruses. Recent studies have revealed that the in vitro antiviral activity of Lf is also extendable to SARS-CoV-2. In vivo, Lf oral administration in early stage of SARS-CoV-2 infection counteracts COVID-19 pathogenesis. In particular, the effect of Lf on SARS-CoV-2 entry, inflammatory homeostasis, iron dysregulation, iron-proteins synthesis, reactive oxygen formation, oxidative stress, gut-lung axis regulation as well as on RNA negativization, and coagulation/fibrinolysis balance will be critically reviewed. Moreover, the molecular mechanisms underneath, including the Lf binding to HSPGs and spike glycoprotein, will be disclosed and discussed. Taken together, present data not only support the application of the oral administration of Lf alone in asymptomatic COVID-19 patients or as adjuvant of standard of care practice in symptomatic ones but also constitute the basis for enriching the limited literature on Lf effectiveness for COVID-19 treatment.

Potential of Lactoferrin in the Treatment of Lung Diseases

“…Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by SARS-CoV-2 virus infection, a highly pathogenic single-stranded (positive) RNA virus belonging to the β-coronavirus family responsible for the COVID-19 pandemic [ 91 , 92 , 93 ]. It mainly infects a person’s respiratory tract, causing fever, fatigue, headache and muscle aches, dry cough, and shortness of breath.…”

A comprehensive review on lactoferrin: a natural multifunctional glycoprotein

“…So, Lf protects the gastrointestinal tract by exerting antiinflammatory activity through maintaining a balance between good and bad gut microbes and reducing the intestinal damage caused by the SARS-CoV-2 virus. 63 In a meta-analysis it was revealed that Lf reduces the risk of respiratory tract infections, so it can be used as an adjunct for the prevention and management of COVID-19. 72 In vitro studies reported that due to the availability, safety, and in vitro efficacy, Lf has protective effects against SARS-CoV-2 by modulating the antiviral immune response with a modest effect on infection.…”

“…So, Lf protects the gastrointestinal tract by exerting anti-inflammatory activity through maintaining a balance between good and bad gut microbes and reducing the intestinal damage caused by the SARS-CoV-2 virus. 63…”

Antimicrobial peptides for novel antiviral strategies in the current post‐COVID‐19 pandemic

“…In addition, several authors have shown how bovine LF can interfere with SARS-CoV and SARS-CoV-2 infections in vitro by enhancing natural killer cell and neutrophil activities. In silico studies have further suggested a possible mechanism of action based on a direct binding of LF to SARS-CoV-2 S glycoprotein and inhibition of the virus access into host cells by competing for ACE binding 130,131.…”