title: A molecular modeling based screening for potential inhibitors to alpha hemolysin from Staphylococcus aureus.
abstract: Staphylococcus aureus, a Gram-positive bacterium is pathogenic in nature. It is known that secreted toxins remain active after antibiotic treatment. The alpha hemolysin or alpha toxin damages cell membrane and induces apoptosis and degradation of DNA. The titer of alphahemolysin increases and causes hemostasis disturbances, thrombocytopenia, and pulmonary lesions during staphylococcal infection. Therefore, it is of interest to inhibit alpha hemolysin using novel compounds. We used the structure of alpha hemolysin(PDB: 7AHL) to screen structures for 100,000 compounds from the ZINC database using molecular docking with AutoDock VINA. Nine (9) successive hits were then subjected for pharmacokinetic and toxicity properties by PROTOX (a webserver for the prediction of oral toxicities of small molecules) and FAFDrugs (a tool for prediction of ADME and Toxicity). This exercise further identified hit #1 ({[3a-(Dihydroxymethyl)-6-hydroxy-2,2-dimethyl-1,3,4-trioxatetrahydro-2H-pentalen-5- yl]methyl}amino(9H-fluoren-9-yl)acetate with binding affinity: -10.3 kcal/mol) and hit #2 (6-(Dihydroxymethyl)-2-{2-[3- (methylamino)propyl]-2-azatricyclo[9.4.0.03,8]pentadeca-1(11),3,5,7,12,14-hexaen-6-yloxy}tetrahydro-2H-pyran-3,4,5-triol with binding affinity: -9.6 kcal/mol) with acceptable toxicity and ADME properties for potential predicted hemolysin inhibition. These compounds should then be evaluated in vitro using inhibitory studies.
authors.affiliation: ViraVigene Research Institute, Tehran, Iran.
authors.forename: Behnam
authors.initials: B
authors.lastname: Rashidieh
authors.affiliation: ViraVigene Research Institute, Tehran, Iran.
authors.forename: Sarah
authors.initials: S
authors.lastname: Etemadiafshar
authors.affiliation: ViraVigene Research Institute, Tehran, Iran.
authors.forename: Golnaz
authors.initials: G
authors.lastname: Memari
authors.affiliation: ViraVigene Research Institute, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Mirzaeichegeni
authors.affiliation: ViraVigene Research Institute, Tehran, Iran.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Yazdi
authors.affiliation: ViraVigene Research Institute, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Farsimadan
authors.affiliation: ViraVigene Research Institute, Tehran, Iran.
authors.forename: Soodabeh
authors.initials: S
authors.lastname: Alizadeh
keywords: Alpha toxin; AutoDock; Molecular docking; Staphylococcus aureus; Virtual screening