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Theranostics 2023; 13(6):1843-1859. doi:10.7150/thno.83522 This issue Cite

Research Paper

Selenium-ruthenium complex blocks H1N1 influenza virus-induced cell damage by activating GPx1/TrxR1

Yinghua Li¹, Danyang Chen¹, Jingyao Su¹, Mingkai Chen², Tianfeng Chen^2✉, Wei Jia^3✉, Bing Zhu^1✉

1. Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China
2. Department of Chemistry, Jinan University, Guangzhou 510632, China
3. Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China

✉ Corresponding authors: Bing Zhu, Address: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China. Phone: +86-020-81330740; Fax: +86-020-81330740; E-mail: zhubingedu.cn; Wei Jia, Address: Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China. Phone: +86-020-38076043; Fax: +86-020-38076043; E-mail: jiawei198044com; Tianfeng Chen, Address: Department of Chemistry, Jinan University, Guangzhou 510632, China. Phone: +86-020-85225962; Fax: +86-020- 85225962; E-mail: tchentfedu.cn. More

Abstract

Background: Influenza A (H1N1) virus is an acute respiratory infectious disease that causes massive morbidity and mortality worldwide. As an essential trace element, selenium is widely applied in the treatment of various diseases because of its functions of enhancing immune response, antioxidant and antiviral mutation. In this study, we constructed the selenium-containing metal complex drug delivery system Ru(biim)(PhenSe)₂ (RuSe), and investigated the anti-influenza virus efficacy and the potential antiviral mechanism for RuSe.

Methods: The inhibitory effect of RuSe on influenza-mediated apoptosis was examined by cell count assay, cell cycle assay, Annenxin-V assay, TUNEL-DAPI assay and reactive oxygen species level determination. Virulence assay, PCR and neuraminidase inhibition assay revealed the inhibition of RuSe on influenza virus. At the level of animal experiments, two animal models were used to clarify the role of RuSe through HE staining, immunohistochemical staining, cytokine determination, selenium metabolism determination and selenium protein expression level determination.

Results: The results of this study confirm that RuSe enhances the expression levels of selenium proteins GPx1 and TrxR1 by regulating selenium metabolism, thereby inhibiting viral replication and assembly and regulating virus-mediated mitochondria-related apoptosis. On the other hand, animal experiments show that RuSe can reduce lung tissue inflammation and inhibit lung tissue cell apoptosis in mice, and improve the survival state of mice. In addition, RuSe significantly improves the low immune response of Se-deficient mice by regulating selenium metabolism, and effectively alleviated lung fibrosis and lung tissue apoptosis in Se-deficient mice.

Conclusions: This study suggests that RuSe provides a promising new approach for the clinical treatment of influenza virus.

Keywords: ruthenium-selenium complexes, H1N1, ROS, selenoprotein, apoptosis

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