title: Modeling of babesipain-1 and identification of natural and synthetic leads for bovine babesiosis drug development.
abstract: Babesiosis is a tick-borne, zoonotic disease caused by species of the intraerythrocytic protozoan Babesia. It is distributed all around the world and affects various domestic and wild animals, mainly cattle. Recently, the cysteine protease enzyme, babesipain-1 from Babesia bigemina has been identified as a potential target for designing new anti-babesiosis drugs. In the present study, a three-dimensional structural model of babesipain-1 was developed. An active site with three pockets (S1, S2, and S3), which is congruent with its homolog, falcipain-3, was also identified. Moreover, the conservation of active site residues was consistent with the cysteine protease family. In order to identify potential inhibitors, a virtual screening workflow was employed with a chemical library containing natural and synthetic compounds. Potential inhibitors interacting with all the three subsites were identified. Further, molecular dynamic simulations were carried out to assess the interactions and stability of the inhibitors. The informatics approach, and the findings presented in this study will assist researchers in further development of potential anti-babesiosis molecules.
authors.affiliation: Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, 500046, India.
authors.forename: Potshangbam Angamba
authors.initials: PA
authors.lastname: Meetei
authors.affiliation: Bioinformatics Infrastructure Facility, School of Life sciences, University of Hyderabad, Hyderabad, 500046, India.|Centre for Biological Sciences, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Patna, 800 014, India.
authors.forename: R S
authors.initials: RS
authors.lastname: Rathore
authors.affiliation: Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, 500046, India.
authors.forename: N Prakash
authors.initials: NP
authors.lastname: Prabhu
authors.affiliation: Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, 500046, India. vvls@uohyd.ernet.in.|Bioinformatics Infrastructure Facility, School of Life sciences, University of Hyderabad, Hyderabad, 500046, India. vvls@uohyd.ernet.in.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Vindal
mesh_terms: D000595:Amino Acid Sequence; D000981:Antiprotozoal Agents / Q000737:chemistry*; D001403:Babesia / Q000187:drug effects; D020134:Catalytic Domain; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000737:chemistry; D057056:Cysteine Proteases / Q000737:chemistry*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry*; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016415:Sequence Alignment; D054852:Small Molecule Libraries / Q000737:chemistry*; D040681:Structural Homology, Protein; D014584:User-Computer Interface
chemical_list: D000981:Antiprotozoal Agents; D015853:Cysteine Proteinase Inhibitors; D015800:Protozoan Proteins; D054852:Small Molecule Libraries; D057056:Cysteine Proteases; D003546:Cysteine Endopeptidases; C443101:falcipain 3
keywords: Babesipain-1; Homology modeling; Molecular docking; Molecular dynamics simulation; Virtual screening