Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 10; p. 1352
• Main Authors: Alves, Nathalia S, Azevedo, Adriana S, Dias, Brenda M, Horbach, Ingrid S, Setatino, Bruno P, Denani, Caio B, Schwarcz, Waleska D, Lima, Sheila Maria B, Missailidis, Sotiris, Ano Bom, Ana Paula D, Silva, Andréa M. V, Barreto Vieira, Débora F, Silva, Marcos Alexandre N, Barros, Caroline A, Carvalho, Carlos Alberto M, Gonçalves, Rafael B
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 25.09.2023; MDPI
• Subjects: antiviral activity; Antiviral agents; Brief Report; Cells; Chemical properties; COVID-19; Disease transmission; Heparan sulfate; Infection; Infections; Kidneys; lactoferrin; Lactoferrins; Mutation; Pandemics; Proteins; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Structure; Testing; Viruses; Brazil; United States > US
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph16101352

Despite the rapid mass vaccination against COVID-19, the emergence of new SARS-CoV-2 variants of concern, such as omicron, is still a great distress, and new therapeutic options are needed. Bovine lactoferrin (bLf), a multifunctional iron-binding glycoprotein available in unsaturated (apo-bLf) and saturated (holo-bLf) forms, has been shown to exert broad-spectrum antiviral activity against many viruses. In this study, we evaluated the efficacy of both forms of bLf at 1 mg/mL against infection of Vero cells by SARS-CoV-2. As assessed with antiviral assays, an equivalent significant reduction in virus infection by about 70% was observed when either form of bLf was present throughout the infection procedure with the SARS-CoV-2 ancestral or omicron strain. This inhibitory effect seemed to be concentrated during the early steps of virus infection, since a significant reduction in its efficiency by about 60% was observed when apo- or holo-bLf were incubated with the cells before or during virus addition, with no significant difference between the antiviral effects of the distinct iron-saturation states of the protein. However, an ultrastructural analysis of bLf treatment during the early steps of virus infection revealed that holo-bLf was somewhat more effective than apo-bLf in inhibiting virus entry. Together, these data suggest that bLf mainly acts in the early events of SARS-CoV-2 infection and is effective against the ancestral virus as well as its omicron variant. Considering that there are no effective treatments to COVID-19 with tolerable toxicity yet, bLf shows up as a promising candidate.