Discovery of a Potential Molluscicide Based on Protein PcRoo in Gill Cilia of Pomacea canaliculata.

Abstract

In modern pesticide discovery, target-based drug design is an attractive and cost-effective approach. Previous studies found that protein rootletin (PcRoo) is a target protein of arecoline, when interacted with Pomacea canaliculata. In this study, we modeled the target protein through threading, and the binding energy between arecoline and protein PcRoo was calculated as -5.02 kcal/mol by molecular docking. Furthermore, two target compounds, baclofen and acedoben, with molluscicidal activity in theory were obtained by virtual screening in database DrugBank. The in vivo bioassay showed that baclofen could induce typical poisoning symptoms on P. canaliculata, which were characterized by weakness of foot muscles and loss of gill cilia, and the LC50 value was 16.2437 mg/L (72 h). Additionally, after 15 mg/L baclofen treatment, the oxygen consumption rate, ammonia excretion rate, and oxygen nitrogen ratio of P. canaliculata declined. Furthermore, the treatment of baclofen also decreased the gene expression level of PcRoo. These trends were the same as the changes after 5 mg/L arecoline treatment. The pharmacophore characteristics were further analyzed, and the results showed that the chemical structures of baclofen and arecoline were correlated in molluscicidal activity. These findings indicate that baclofen has the potential to be used as a molluscicide in agricultural production, and other new molluscicides may be obtained by virtual screening based on protein PcRoo.