tetano
Editor, Senior Moderator
Antiviral Res
. 2022 Nov 16;105465.
doi: 10.1016/j.antiviral.2022.105465. Online ahead of print.
In vitro and in vivo effects of 3-indoleacetonitrile-A potential new broad-spectrum therapeutic agent for SARS-CoV-2 infection
Xianfeng Hui[SUP] 1 [/SUP], Xiao Yu[SUP] 2 [/SUP], Kun Huang[SUP] 1 [/SUP], Ting Xu[SUP] 1 [/SUP], Lei Cao[SUP] 1 [/SUP], Yufei Zhang[SUP] 1 [/SUP], Lianzhong Zhao[SUP] 1 [/SUP], Ya Zhao[SUP] 1 [/SUP], Changjie Lv[SUP] 1 [/SUP], Sheng Feng[SUP] 3 [/SUP], Yongzhong Jiang[SUP] 2 [/SUP], Linlin Liu[SUP] 4 [/SUP], Meilin Jin[SUP] 5 [/SUP]
Affiliations
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.
. 2022 Nov 16;105465.
doi: 10.1016/j.antiviral.2022.105465. Online ahead of print.
In vitro and in vivo effects of 3-indoleacetonitrile-A potential new broad-spectrum therapeutic agent for SARS-CoV-2 infection
Xianfeng Hui[SUP] 1 [/SUP], Xiao Yu[SUP] 2 [/SUP], Kun Huang[SUP] 1 [/SUP], Ting Xu[SUP] 1 [/SUP], Lei Cao[SUP] 1 [/SUP], Yufei Zhang[SUP] 1 [/SUP], Lianzhong Zhao[SUP] 1 [/SUP], Ya Zhao[SUP] 1 [/SUP], Changjie Lv[SUP] 1 [/SUP], Sheng Feng[SUP] 3 [/SUP], Yongzhong Jiang[SUP] 2 [/SUP], Linlin Liu[SUP] 4 [/SUP], Meilin Jin[SUP] 5 [/SUP]
Affiliations
- PMID: 36402240
- PMCID: PMC9671535
- 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.