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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2025-06-01
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| Online Access: | https://www.mdpi.com/1999-4915/17/7/873 |
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| author | Yinde Gan Fucheng Guo Ayan Roy Xiao Wang Yongyi Shen |
| author_facet | Yinde Gan Fucheng Guo Ayan Roy Xiao Wang Yongyi Shen |
| author_sort | Yinde Gan |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| institution | Matheson Library |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-320e8a4f45804591a9d042fdbf3cd8d52025-07-25T13:38:44ZengMDPI AGViruses1999-49152025-06-0117787310.3390/v17070873Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza VirusYinde Gan0Fucheng Guo1Ayan Roy2Xiao Wang3Yongyi Shen4State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaDepartment of Biological Sciences, Asian University for Women, Chittagong 4000, BangladeshState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaThe 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.https://www.mdpi.com/1999-4915/17/7/873mangiferininfluenza virus A(H1N1)pdm09molecular docking |
| spellingShingle | Yinde Gan Fucheng Guo Ayan Roy Xiao Wang Yongyi Shen Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza Virus Viruses mangiferin influenza virus A(H1N1)pdm09 molecular docking |
| title | Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza Virus |
| title_full | Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza Virus |
| title_fullStr | Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza Virus |
| title_full_unstemmed | Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza Virus |
| title_short | Integrated In Silico, In Vitro, and In Vivo Studies Reveal Mangiferin as a Promising Antiviral Agent Against H1N1/pdm2009 Influenza Virus |
| title_sort | integrated in silico in vitro and in vivo studies reveal mangiferin as a promising antiviral agent against h1n1 pdm2009 influenza virus |
| topic | mangiferin influenza virus A(H1N1)pdm09 molecular docking |
| url | https://www.mdpi.com/1999-4915/17/7/873 |
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