2. Academic Validation
  3. In vitro and in vivo effects of 3-indoleacetonitrile-A potential new broad-spectrum therapeutic agent for SARS-CoV-2 infection

In vitro and in vivo effects of 3-indoleacetonitrile-A potential new broad-spectrum therapeutic agent for SARS-CoV-2 infection

  • Antiviral Res. 2023 Jan:209:105465. doi: 10.1016/j.antiviral.2022.105465.
Xianfeng Hui 1,  Xiao Yu 2,  Kun Huang 1,  Ting Xu 1,  Lei Cao 1,  Yufei Zhang 1,  Lianzhong Zhao 1,  Ya Zhao 1,  Changjie Lv 1,  Sheng Feng 3,  Yongzhong Jiang 2,  Linlin Liu 4,  Meilin Jin 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; College of Animal Medicine, Huazhong Agricultural University, Wuhan, China.
  • 2 Institute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.
  • 3 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
  • 4 Institute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China. Electronic address: mice0809@163.com.
  • 5 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; College of Animal Medicine, Huazhong Agricultural University, Wuhan, China. Electronic address: jml8328@126.com.
PMID: 36402240 DOI: 10.1016/j.antiviral.2022.105465
Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has resulted in significant global morbidity, mortality, and societal disruption. Currently, effective Antiviral drugs for the treatment of SARS-CoV-2 Infection are limited. Therefore, safe and effective Antiviral drugs to combat COVID-19 are urgently required. In previous studies, we showed that 3-indoleacetonitrile, a plant growth hormone produced by cruciferous (Brassica) vegetables, is effective in treating influenza A virus Infection. However, the molecular mechanisms underlying these effects remain unclear. Herein, we demonstrated that 3-indoleacetonitrile exhibits broad-spectrum Antiviral activity and is effective against HSV-1 and VSV infections in vitro. This phenomenon prompted us to study its role in the anti-SARS-CoV-2 process. Interestingly, 3-indoleacetonitrile exhibited Antiviral activity against SARS-CoV-2 in vitro. Importantly, tail vein injection of 3-indoleacetonitrile resulted in good Antiviral activity in mouse models infected with WBP-1 (a mouse adaptation of the SARS-CoV-2 strain). Mechanistically, 3-indoleacetonitrile promoted the host interferon signalling pathway response and inhibited autophagic flux. Furthermore, we demonstrated that 3-indoleacetonitrile induced an increase in mitochondrial antiviral-signalling (MAVS) protein levels, which might be attributed to its inhibition of the interaction between MAVS and the selective Autophagy receptor SQSTM1. Overall, our results demonstrate that 3-indoleacetonitrile is potently active against SARS-CoV-2 in vitro and in vivo, which may provide a foundation for further clinical testing for the treatment of COVID-19. In addition, considering its broad-spectrum Antiviral effect, it should be explored whether it also has an effect on Other viruses that threaten human health.

Keywords

3-Indoleacetonitrile; Broad-spectrum antiviral efficacy; IFN; SARS-CoV-2.

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