9-Butyl-Harmol Exerts Antiviral Activity against Newcastle Disease Virus through Targeting GSK-3β and HSP90β
Chongyang Wang, Ting Wang, Ruochen Hu, Liuyuan Duan, Qili Hou, Han Yu, Jiangkun Dai, Wenbin Wang, Shanhui Ren, Haijin Liu, Xinglong Wang, Sa Xiao, Na Li, Junru Wang, Zengqi Yang
Abstract
Paramyxoviruses cause devastating impacts on health and the economy worldwide. However, there are no suitable drugs with which to counteract the viruses. We determined that 9-butyl-harmol could serve as a potential antiviral agent against paramyxoviruses. Until now, the antiviral mechanism of β-carboline derivatives against RNA viruses has rarely been studied. Here, we found that 9-butyl-harmol exerts dual mechanisms of antiviral action, with its antiviral activities being mediated by two targets: GSK-3β and HSP90β. Correspondingly, the interaction between NDV infection and the Wnt/β-catenin pathway or HSP90 is demonstrated in this study. Taken together, our findings shed light on the development of antiviral agents against paramyxoviruses, based on the β-carboline scaffold. These results present mechanistic insights into the polypharmacology of 9-butyl-harmol. Understanding this mechanism also deepens the host-virus interaction and reveals new drug targets for anti-paramyxoviruses.