1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes
Newcastle disease virus (NDV) is one of the highly contagious pathogens causing devastating economic effects on the global poultry industry. In the present study, three 1-formyl-<i>β</i>-carboline derivatives (compounds <b>6</b>, <b>7</b>, and <b>9</b>...
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2021
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oai:doaj.org-article:f759be8e34dc4505874a78567be50b5f2021-11-25T16:53:49Z1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes10.3390/biom111116872218-273Xhttps://doaj.org/article/f759be8e34dc4505874a78567be50b5f2021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1687https://doaj.org/toc/2218-273XNewcastle disease virus (NDV) is one of the highly contagious pathogens causing devastating economic effects on the global poultry industry. In the present study, three 1-formyl-<i>β</i>-carboline derivatives (compounds <b>6</b>, <b>7</b>, and <b>9</b>) were found to be potent inhibitors of different genotypes of NDV with IC<sub>50</sub> values within 10 μM, which are similar to ribavirin. The virus titers were decreased by the presence of 1-formyl-<i>β</i>-carboline derivatives in a dose-dependent manner, and the inhibition rate was found to exceed 90% at the concentration of 20 μM. These compounds mainly suppressed the adsorption and entry processes of NDV lifecycle. Through DARTS, CETSA, and RBC binding assay, these compounds were identified as novel HN inhibitors, which could directly interact with the NDV HN protein to affect the adsorption of NDV. Furthermore, they could inhibit the entry of NDV through suppressing the PI3K/Akt pathway rather than the ERK pathway. The PI3K/Akt pathway was proved to be involved in NDV entry. Our findings reveal a unique mechanism through which 1-formyl-<i>β</i>-carboline derivatives restrain NDV infection. Moreover, these compounds represent suitable scaffolds for designing novel HN inhibitors.Chongyang WangTing WangJiangkun DaiZhiyuan AnRuochen HuLiuyuan DuanHui ChenXiangwei WangZhili ChuHaijin LiuJuan WangNa LiZengqi YangJunru WangMDPI AGarticle<i>β</i>-carbolinesanti-viral activityNewcastle disease virusHN proteinPI3K/Akt signaling pathwayMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1687, p 1687 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
<i>β</i>-carbolines anti-viral activity Newcastle disease virus HN protein PI3K/Akt signaling pathway Microbiology QR1-502 |
| spellingShingle |
<i>β</i>-carbolines anti-viral activity Newcastle disease virus HN protein PI3K/Akt signaling pathway Microbiology QR1-502 Chongyang Wang Ting Wang Jiangkun Dai Zhiyuan An Ruochen Hu Liuyuan Duan Hui Chen Xiangwei Wang Zhili Chu Haijin Liu Juan Wang Na Li Zengqi Yang Junru Wang 1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes |
| description |
Newcastle disease virus (NDV) is one of the highly contagious pathogens causing devastating economic effects on the global poultry industry. In the present study, three 1-formyl-<i>β</i>-carboline derivatives (compounds <b>6</b>, <b>7</b>, and <b>9</b>) were found to be potent inhibitors of different genotypes of NDV with IC<sub>50</sub> values within 10 μM, which are similar to ribavirin. The virus titers were decreased by the presence of 1-formyl-<i>β</i>-carboline derivatives in a dose-dependent manner, and the inhibition rate was found to exceed 90% at the concentration of 20 μM. These compounds mainly suppressed the adsorption and entry processes of NDV lifecycle. Through DARTS, CETSA, and RBC binding assay, these compounds were identified as novel HN inhibitors, which could directly interact with the NDV HN protein to affect the adsorption of NDV. Furthermore, they could inhibit the entry of NDV through suppressing the PI3K/Akt pathway rather than the ERK pathway. The PI3K/Akt pathway was proved to be involved in NDV entry. Our findings reveal a unique mechanism through which 1-formyl-<i>β</i>-carboline derivatives restrain NDV infection. Moreover, these compounds represent suitable scaffolds for designing novel HN inhibitors. |
| format |
article |
| author |
Chongyang Wang Ting Wang Jiangkun Dai Zhiyuan An Ruochen Hu Liuyuan Duan Hui Chen Xiangwei Wang Zhili Chu Haijin Liu Juan Wang Na Li Zengqi Yang Junru Wang |
| author_facet |
Chongyang Wang Ting Wang Jiangkun Dai Zhiyuan An Ruochen Hu Liuyuan Duan Hui Chen Xiangwei Wang Zhili Chu Haijin Liu Juan Wang Na Li Zengqi Yang Junru Wang |
| author_sort |
Chongyang Wang |
| title |
1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes |
| title_short |
1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes |
| title_full |
1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes |
| title_fullStr |
1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes |
| title_full_unstemmed |
1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes |
| title_sort |
1-formyl-<i>β</i>-carboline derivatives block newcastle disease virus proliferation through suppressing viral adsorption and entry processes |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/f759be8e34dc4505874a78567be50b5f |
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