Mycoplasma pneumoniae FtsZ homology modeling and Molecular docking Analysis

Abstract: One of the main causes of mortality and morbidity among children globally is respiratory tract infections. Mild tracheobronchitis or severe atypical pneumonia are clinical presentations of Mycoplasma pneumoniae and macrolides are recommended as first-line therapy for children. In the last decade, the widespread emergence of Macrolide-resistant M. pneumoniae is a serious threat to global public health. To counteract this fundamental problem, the bacterial cell division and the crucial proteins involved in this process as FtsZ emerged as novel attractive targets. In this work, we perform a virtual based structure screening against FtsZ protein with several inhibitors, especially medicinal plants derivatives, as a new target for drug developement. Methods: Sequence homology of FtsZ were performed using BLAST and 3D structure was predicted using Swissmodel. Structure based virtual screening was performed to identify the binding affinity and the interactions sites between the complexes using Autodockvina tools. ADMET analysis was performed using Swissadme server. Results: Throught sequence homology, FtsZ shared homology of 56 % with M. genitallium. This renderes it a promising target. Natural FtsZ inhibitors were virtually screened, the results showed six compounds (Curcumin, doxorubucine, chlorogenic acid, berberine, sanguinarine and plumbagin), each with high binding affinity ranging from -6.6 and -8.5 Kcal/mol. The majority of compounds have low toxicity, chlorogenic acid was found as non toxic belongs to the class VI. Conclusions: M. pneumoniae FtsZ protein is a promising target for drug screening. Six compounds showed high affinity and could provide new options for the treatment of Macrolide-resistant M. pneumoniae.