Discovery of FtsZ inhibitors by virtual screening as antibacterial agents and study of the inhibition mechanism

Inhibition of bacterial cell division is a novel mechanistic action in the development of new antimicrobial agents. The FtsZ protein is an important antimicrobial drug target because of its essential role in bacterial cell division. In the present study, potential inhibitors of FtsZ were identified by virtual screening followed by in vivo and in vitro bioassays. One of the candidates, Dacomitinib (S2727), shows for the first time its potent inhibitory activity against the MRSA strains. The binding mode of Dacomitinib in FtsZ was analyzed by docking, and Asp(199) and Thr(265) are thought to be essential residues involved in the interactions.

Automated summary

In this study, potential inhibitors of FtsZ were identified through virtual screening and bioassays, with one candidate, Dacomitinib (S2727), showing potent inhibitory activity against MRSA strains for the first time. The binding mode of Dacomitinib in FtsZ was analyzed by docking, revealing Asp(199) and Thr(265) as essential residues involved in the interactions.