Pharmaceuticals (Sep 2023)

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

  • Nathalia S. Alves,
  • Adriana S. Azevedo,
  • Brenda M. Dias,
  • Ingrid S. Horbach,
  • Bruno P. Setatino,
  • Caio B. Denani,
  • Waleska D. Schwarcz,
  • Sheila Maria B. Lima,
  • Sotiris Missailidis,
  • Ana Paula D. Ano Bom,
  • Andréa M. V. Silva,
  • Débora F. Barreto Vieira,
  • Marcos Alexandre N. Silva,
  • Caroline A. Barros,
  • Carlos Alberto M. Carvalho,
  • Rafael B. Gonçalves

DOI
https://doi.org/10.3390/ph16101352
Journal volume & issue
Vol. 16, no. 10
p. 1352

Abstract

Read online

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.

Keywords