Inhibitory effect of lactoferrin-coated zinc nanoparticles on SARS-CoV-2 replication and entry along with improvement of lung fibrosis induced in adult male albino rats

Int J Biol Macromol. 2023 Aug 1:245:125552. doi: 10.1016/j.ijbiomac.2023.125552. Epub 2023 Jun 24.

Abstract

Severe acute respiratory syndrome 2019-new coronavirus (SARS-CoV-2) is a major global challenge caused by a pandemic disease, named 'COVID-19' with no effective and selective therapy available so far. COVID-19-associated mortality is directly related to the inability to suppress the viral infection and the uncontrolled inflammatory response. So, we investigated the antiviral efficiency of the nanofabricated and well-characterized lactoferrin-coated zinc nanoparticles (Lf-Zn-NPs) on SARS-CoV-2 replication and entry into host cells. Lf-Zn-NPs showed potent inhibition of the entry of SARS-CoV-2 into the host cells by inhibition of ACE2, the SARS-CoV-2 receptor. This inhibitory activity of Lf-Zn-NPs to target the interaction between the SARS-CoV-2 spike protein and the ACE2 receptor offers potent protection against COVID-19 outbreaks. Moreover, the administration of Lf-Zn-NPs markedly improved lung fibrosis disorders, as supported by histopathological findings and monitored by the significant reduction in the values of CRP, LDH, ferritin, and D-dimer, with a remarkable rise in CD4+, lung SOD, GPx, GSH, and CAT levels. Lf-Zn-NPs revealed therapeutic efficiency against lung fibrosis owing to their anti-inflammatory, antioxidant, and ACE2-inhibiting activities. These findings suggest a promising nanomedicine agent against COVID-19 and its complications, with improved antiviral and immunomodulatory properties as well as a safer mode of action.

Keywords: Antiviral activity; Bovine Lactoferrin; COVID-19; Nanoparticles; Pulmonary fibrosis; Zinc oxide.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • COVID-19*
  • Humans
  • Lactoferrin / pharmacology
  • Male
  • Metal Nanoparticles*
  • Pulmonary Fibrosis* / drug therapy
  • Rats
  • SARS-CoV-2
  • Zinc

Substances

  • spike protein, SARS-CoV-2
  • Lactoferrin
  • Angiotensin-Converting Enzyme 2
  • Zinc
  • Antiviral Agents