Abstract
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.
Highlights
The Newcastle disease (ND) is one of the most severe viral diseases in the poultry industry worldwide
The anti-viral activity assays were performed with the corresponding compound at up to
Based on the results of cell viability, the anti-viral activity against Newcastle disease virus (NDV) was screened by plaque assay and Reverse Transcription and Quantitative Real-Time PCR (RT-qPCR) at the concentration without cytotoxicity
Summary
The Newcastle disease (ND) is one of the most severe viral diseases in the poultry industry worldwide. Different anti-viral agents block various steps of the viral life cycle, including host receptor binding, viral entry, replication, assembly, and budding. Destroying the early stage of the virus life cycle, including host receptor binding or viral entry, can effectively inhibit virus proliferation. During NDV infection, the F protein is responsible for virus–cell membrane fusion, assisting viral entry [17,18]. The entry of Vaccinia virus depends on the activation of the PI3K/Akt signalling pathway [18]. The ERK pathway, activated by HSV-1, controls early cofilin phosphorylation and cell ruffle formation to regulate the entry of HSV-1 [19]. Twelve β-carboline derivatives with substituents at C1 , C3 , and C6 were selected for an evaluation of their in vitro anti-viral activity against NDV. Three 1-formyl-β-carboline derivatives were identified as novel NDV inhibitors through suppressing the adsorption and entry processes of the NDV lifecycle
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
