1-Formyl-β-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-beta-carboline derivatives (compounds 6, 7, and 9) were found to be potent inhibitors of different genotypes of NDV with IC50 values within 10 mu M, which are similar to ribavirin. The virus titers were decreased by the presence of 1-formyl-beta-carboline derivatives in a dose-dependent manner, and the inhibition rate was found to exceed 90% at the concentration of 20 mu M. 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-beta-carboline derivatives restrain NDV infection. Moreover, these compounds represent suitable scaffolds for designing novel HN inhibitors.

Automated summary

In this study, three 1-formyl-beta-carboline derivatives were found to be potent inhibitors of NDV, reducing virus titers through suppressing adsorption and entry processes. These compounds are identified as novel HN inhibitors, directly interacting with the NDV HN protein to affect virus adsorption and entry. Additionally, they inhibit NDV entry by suppressing the PI3K/Akt pathway, representing a unique mechanism for restraining NDV infection.