1-Formyl-<i>β</i>-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes
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
Affiliations
Chongyang Wang
College of Chemistry and Pharmacy, Northwest A&F University, Xianyang 712100, China
Ting Wang
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Jiangkun Dai
College of Chemistry and Pharmacy, Northwest A&F University, Xianyang 712100, China
Zhiyuan An
College of Chemistry and Pharmacy, Northwest A&F University, Xianyang 712100, China
Ruochen Hu
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Liuyuan Duan
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Hui Chen
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Xiangwei Wang
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Zhili Chu
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Haijin Liu
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Juan Wang
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Na Li
Instrumental Analysis Center, Xi’an Jiaotong University, Xi’an 710049, China
Zengqi Yang
College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
Junru Wang
College of Chemistry and Pharmacy, Northwest A&F University, Xianyang 712100, China
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-β-carboline derivatives (compounds 6, 7, and 9) were found to be potent inhibitors of different genotypes of NDV with IC50 values within 10 μM, which are similar to ribavirin. The virus titers were decreased by the presence of 1-formyl-β-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-β-carboline derivatives restrain NDV infection. Moreover, these compounds represent suitable scaffolds for designing novel HN inhibitors.
