Title:Molecular Modeling on Streptolysin-O of Multidrug Resistant Streptococcus pyogenes and Computer Aided Screening and In Vitro Assay for Novel Herbal Inhibitors
VOLUME: 10 ISSUE: 1
Author(s):Sinosh Skariyachan, Naik Sowmyalaxmi Narayan, Tejaswini S Aggimath, Sushmitha Nagaraj, Monika S Reddy and Rajeswari Narayanappa
Affiliation:R & D Centre, Department of Biotechnology, Dayananda Sagar College of Engineering, Bangalore, 560 078, Karnataka, India.
Keywords:Streptococcus pyogenes, streptolysin-O, multi-drug resistance, homology model, hemolysis, computer aided
screening, phytoligands.
Abstract:Streptococcus pyogenes is a notorious pathogenic bacterium which causes various human diseases ranging
from localized infections to life threatening invasive diseases. Streptolysin-O (SLO), pore-forming thiol-activated
cytolysin, is the major virulent factor for streptococcal infections. Present therapies against streptococcal infections are
limited as most of the strains have developed multi-drug resistance to present generation of drugs. Hence, there is a need
for alternative therapeutic substances. Structure based virtual screening is a novel platform to select lead molecules with
better pharmacokinetic properties. The 3D structure of SLO (not available in native form), essential for such studies, was
computationally generated and this homology model was used as probable drug target. Based on literature survey, several
phytoligands from 25 medicinal plants were selected. Out of these, leads from 11 plants showed better pharmacokinetic
properties. The best lead molecules were screened based on computer aided drug likeness and pharmacokinetic
predictions. The inhibitory properties of selected herbal leads against SLO were studied by molecular docking. An in vitro
assay was further carried out and variations observed were found to be significant (p<0.05). Antibiotic sensitivity testing
was also performed with the clinical strain of Streptococcus pyogenes with conventional drugs. The clinical strain showed
multi-drug resistance to conventional drugs. Our study revealed that numerous phytoligands have better inhibitory
properties towards the toxin. We noticed that incorporation of selected herbal extracts in blood agar medium showed
significant reduction in hemolysis (MIC 300μl/plate), indicating inhibition of SLO. Furthermore, the butanol extracts of
selected herbal preparation based on computer aided screening showed significant inhibitory properties at 250 mcg/disc
concentration. We also noticed that selected herbal formulations have better antimicrobial properties at MIC range of 300-
400μl. Hence, our study suggests that these herbal extracts have better inhibitory properties against the toxin as well as
drug resistant Streptococcus pyogenes.
