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Biocompatible Iron Oxide Nanoparticles Display Antiviral Activity Against Two Different Respiratory Viruses in Mice
Marta L DeDiego1, Yadileiny Portilla2, Neus Daviu2
1Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
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.
Insights
Iron oxide nanoparticles (DMSA-IONP-10) show promise as a universal antiviral treatment, effectively reducing replication of SARS-CoV-2 and Influenza A viruses in vivo and in vitro.
Area of Science:
- Nanomedicine
- Virology
- Immunology
Background:
- Influenza A virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cause significant respiratory illness with overlapping symptoms.
- Existing antiviral treatments face challenges due to drug resistance and specificity, necessitating novel broad-spectrum therapies.
- Iron oxide nanoparticles (IONPs) coated with dimercaptosuccinic acid (DMSA-IONP-10) have demonstrated in vitro antiviral activity against SARS-CoV-2.
Purpose of the Study:
- To evaluate the in vivo antiviral efficacy of DMSA-IONP-10 against SARS-CoV-2.
- To assess the in vitro and in vivo antiviral activity of DMSA-IONP-10 against Influenza A virus (IAV).
- To explore the potential of DMSA-IONP-10 as a universal therapeutic agent for respiratory viral infections.
Main Methods:
- In vivo studies involved treating SARS-CoV-2 infected mice with DMSA-IONP-10.
- In vitro and in vivo assays were conducted to analyze DMSA-IONP-10's effect on IAV.
- Cytokine induction, viral replication, and cellular oxidative stress/iron metabolism were assessed.
Main Results:
- DMSA-IONP-10 treatment in mice reduced SARS-CoV-2 replication in lungs and modulated pro-inflammatory responses.
- DMSA-IONP-10 exhibited prophylactic and therapeutic effects against IAV in cell cultures and in infected mice, inhibiting viral replication.
- IONP treatment appeared to influence cellular oxidative stress and iron metabolism, potentially impacting viral production and dampening the host's inflammatory response.
Conclusions:
- DMSA-IONP-10 demonstrates significant antiviral activity against both SARS-CoV-2 and IAV.
- These findings highlight the potential of DMSA-IONP-10 as a therapeutic agent for major human respiratory viruses.
- The study underscores the therapeutic potential of IONPs in combating viral respiratory infections.
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