title: Insilico studies on anthrax lethal factor inhibitors: pharmacophore modeling and virtual screening approaches towards designing of novel inhibitors for a killer.
abstract: Bacillus anthracis is a causative organism of anthrax. The main reason to use anthrax as a bioweapon is the combination of the spore's durability and the lethal toxaemia of the vegetative stage. In anthrax infection, lethal factor (LF) is playing crucial role in causing cell death, by inhibiting pathways that rely on this kinase family. The combination of vaccine and antibiotics is preferred as an effective treatment for this target. Till date, no small molecule inhibitor is identified as a drug on the target. In this study, we have performed pharmacophore modeling and docking studies to identify a novel small molecule inhibitor to target the Anthrax LF. The best pharmacophore model is used to screen approximately 2M drug-like small molecule database and yielded 2543 hits. Docking studies of the pharmacophore hits on to the active site of Anthrax LF resulted 120 structurally diverse hits. Out of 120 hits, based on synthetic feasibility, 17 hits are selected for further synthesis and pharmacological screening. In due course, we will publish the updated results.
authors: BioCampus, GVKBIO Sciences Private Limited, S-1, Phase-1, TIE, Balanagar, Hyderabad 500037, AP, India.
authors: Jyoti
authors: J
authors: Roy
authors: Uday Chandra
authors: UC
authors: Kumar
authors: Pavan Kumar
authors: PK
authors: Machiraju
authors: Ravi Kumar
authors: RK
authors: Muttineni
authors: Suneel
authors: S
authors: Kumar B V S
authors: Rambabu
authors: R
authors: Gundla
authors: Raveendra
authors: R
authors: Dayam
authors: Jagarlapudi A R P
authors: JA
authors: Sarma
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry; D000992:Antitoxins / Q000737:chemistry* / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D014584:User-Computer Interface
chemical_list: D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D008024:Ligands; C030325:anthrax toxin