Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza Virus
The ongoing global threat posed by the influenza A virus, exacerbated by antigenic drift and the emergence of antiviral resistance, accentuates the urgent need for innovative therapeutic strategies. Through molecular docking, this study revealed that mangiferin has a strong binding affinity for the...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/17/7/873 |
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| Summary: | The ongoing global threat posed by the influenza A virus, exacerbated by antigenic drift and the emergence of antiviral resistance, accentuates the urgent need for innovative therapeutic strategies. Through molecular docking, this study revealed that mangiferin has a strong binding affinity for the active site of the neuraminidase (NA) protein of influenza virus A(H1N1)pdm09, with a binding energy of −8.1 kcal/mol. In vitro assays confirmed a dose-dependent inhibition of NA, with an IC<sub>50</sub> of 88.65 μM, and minimal cytotoxicity, as indicated by a CC<sub>50</sub> of 328.1 μM in MDCK cells. In murine models, the administration of mangiferin at a dosage of 25 mg/kg significantly mitigated weight loss, decreased viral loads in nasal turbinates and lungs by over 1 log10 TCID<sub>50</sub>, and enhanced survival rates from 0% in control groups to 20% in mangiferin-treated group at 14 days post-infection. In addition, mangiferin was found to modulate host immune responses by simultaneously inhibiting pro-inflammatory cytokines, IL-6 and TNF-α, and upregulating the expression of anti-inflammatory IL-10 and antiviral IFN-γ, thus mitigating infection-induced inflammation. Our findings elucidate the dual mechanism of mangiferin involving the direct inhibition of NA and immunomodulation, thereby providing experimental evidence for exploring dual-mechanism-based anti-influenza strategies against resistant strains of influenza. |
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| ISSN: | 1999-4915 |