3-Indoleacetonitrile Is Highly Effective in Treating Influenza A Virus Infection In Vitro and In Vivo
Xuejin Zhao,
Lianzhong Zhao,
Ya Zhao,
Kun Huang,
Wenxiao Gong,
Ying Yang,
Li Zhao,
Xiaohan Xia,
Zaiyun Li,
Feng Sheng,
Xuezhu Du,
Meilin Jin
Affiliations
Xuejin Zhao
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China
Lianzhong Zhao
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
Ya Zhao
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
Kun Huang
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
Wenxiao Gong
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
Ying Yang
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
Li Zhao
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China
Xiaohan Xia
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China
Zaiyun Li
National Key Lab of Crop Genetic Improvement, National Center of Oil Crop Improvement (Wuhan), College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
Feng Sheng
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China
Xuezhu Du
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China
Meilin Jin
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
Influenza A viruses are serious zoonotic pathogens that continuously cause pandemics in several animal hosts, including birds, pigs, and humans. Indole derivatives containing an indole core framework have been extensively studied and developed to prevent and/or treat viral infection. This study evaluated the anti-influenza activity of several indole derivatives, including 3-indoleacetonitrile, indole-3-carboxaldehyde, 3-carboxyindole, and gramine, in A549 and MDCK cells. Among these compounds, 3-indoleacetonitrile exerts profound antiviral activity against a broad spectrum of influenza A viruses, as tested in A549 cells. Importantly, in a mouse model, 3-indoleacetonitrile with a non-toxic concentration of 20 mg/kg effectively reduced the mortality and weight loss, diminished lung virus titers, and alleviated lung lesions of mice lethally challenged with A/duck/Hubei/WH18/2015 H5N6 and A/Puerto Rico/8/1934 H1N1 influenza A viruses. The antiviral properties enable the potential use of 3-indoleacetonitrile for the treatment of IAV infection.
