Biocompatible Iron Oxide Nanoparticles Display Antiviral Activity Against Two Different Respiratory Viruses in Mice

Int J Nanomedicine. 2024 Dec 21:19:13763-13788. doi: 10.2147/IJN.S475323. eCollection 2024.

Abstract

Background: Severe Acute Respiratory syndrome coronavirus 2 (SARS-CoV-2) and Influenza A viruses (IAVs) are among the most important causes of viral respiratory tract infections, causing similar symptoms. IAV and SARS-CoV-2 infections can provoke mild symptoms like fever, cough, sore throat, loss of taste or smell, or they may cause more severe consequences leading to pneumonia, acute respiratory distress syndrome or even death. While treatments for IAV and SARS-CoV-2 infection are available, IAV antivirals often target viral proteins facilitating the emergence of drug-resistant viral variants. Hence, universal treatments against coronaviruses and IAVs are hard to obtain due to genus differences (in the case of coronavirus) or subtypes (in the case of IAV), highlighting the need for novel antiviral therapies. Interestingly, iron oxide nanoparticles (IONPs) with a 10 nm core size and coated with the biocompatible dimercaptosuccinic acid (DMSA: DMSA-IONP-10) display antiviral activity against SARS-CoV-2 in vitro.

Methods: We analyzed the antiviral activity of DMSA-IONP-10 against SARS-CoV-2 infection in vivo, and against IAV infection in vitro and in vivo.

Results: DMSA-IONP-10 treatment of mice after SARS-CoV-2 infection impaired virus replication in the lungs and led to a mildly reduced pro-inflammatory cytokine induction after infection, indicating that these IONPs can serve as COVID-19 therapeutic agents. These IONPs also had a prophylactic and therapeutic effect against IAV in tissue cultured cells at non-cytotoxic doses, and a therapeutic effect in IAV-infected-mice, inhibiting viral replication and slightly dampening the inflammatory response after viral infection. As an exacerbated inflammatory response to IAVs and SARS-CoV-2 is detrimental to the host, weakening this response in mice through IONP treatment may reduce disease severity. Interestingly, our data suggest that IONP treatment affects oxidative stress and iron metabolism in cells, which may influence IAV production.

Conclusion: This study highlights the antiviral activity of DMSA-IONP-10 against important human respiratory viruses.

Keywords: IAV; SARS-CoV-2; iron metabolism; iron oxide nanoparticles; oxidative stress; viral infection.

MeSH terms

  • A549 Cells
  • Animals
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Chlorocebus aethiops
  • Dogs
  • Female
  • Humans
  • Influenza A virus / drug effects
  • Influenza A virus / physiology
  • Madin Darby Canine Kidney Cells
  • Magnetic Iron Oxide Nanoparticles / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / virology
  • SARS-CoV-2* / drug effects
  • Succimer / chemistry
  • Succimer / pharmacology

Substances

  • Antiviral Agents
  • Succimer
  • Biocompatible Materials

Grants and funding

This work was supported by the Spanish National Research Council Interdisciplinary Thematic Platform (PTI) Global Health (PTI Salud Global) [CSIC-COV19-012/012202020E154]; the European Commission-NextGenerationEU (Regulation EU2020/2094) through CSIC’s Global Health Platform (PTI Salud Global) [SGL2103021]; the MCIN/AEI/10.13039/501100011033 and the “European Union NextGenerationEU/PRTR” [PDC2021-120759-I00]; the MCIN/AEI/10.13039/501100011033 [PID2020-112685RB-I00 and PID2020-113480RB-I00]; the MCIU/AEI/10.13039/501100011033 and FEDER, EU [PID2023-146212OB-I00]; the “Atracción de Talento Investigador” programme funded by the “Comunidad de Madrid” [2017-T1/BMD-515]; the Marie Skłodowska-Curie Actions programme (EU) [101007629-NESTOR-H2020-MSCARISE-2020]. In relation to the work presented here, Y. Portilla was first a predoctoral FPU scholar [FPU15/06170] funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”, then a predoctoral scholar funded by CSIC-COV19-012/012202020E154, and finally, a postdoctoral scholar funded by the European Commission-NextGenerationEU (Regulation EU2020/2094) through the CSIC’s Global Health Platform (PTI Salud Global) [SGL2103021]. P. Vázquez-Utrilla was a predoctoral scholar funded by the European Commission-NextGenerationEU (Regulation EU2020/2094) through the CSIC’s Global Health Platform (PTI Salud Global) [SGL2103012]. V. Mulens-Arias was a postdoctoral scholar working under a Juan de La Cierva-Incorporación Contract [IJCI-2017-31447] funded by MCIN/AEI/10.13039/501100011033. N. Daviu was a predoctoral scholar [FPU18/04828] funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”. The project that gave rise to these results received the support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/DR22/11950020 (to D. López-García). This research work was performed in the framework of the Nanomedicine CSIC HUB (ref: 202180E048).