title: In silico analysis and prioritization of drug targets in Fusarium solani.
abstract: Mycotic keratitis has emerged as a major ophthalmic problem and a leading cause of blindness, since its recognition in 1879. Filamentous fungi are major causative of mycotic keratitis. In India, the main etiological organism responsible for mycotic keratitis is Aspergillus species followed by Fusarium species. In South India, Fusarium based keratitis scales up to 43%. Nearly one-third of mycotic keratitis treatment results in failure, as fungal infections are highly resistant to antibiotic therapies. Therefore, there is need to determine novel and specific targets to constrain Fusarium infections in human eye. In this study, we implemented subtractive proteomics coupled with in silico functional annotation to prioritize potential and specific drug targets which can be used to modulate the virulence of Fusarium solani subsp.pisi (Nectria haematococca MPVI). The results infer that Thiamine thiazole synthase (Thi4), an intracellular membrane bound protein as the potential target, which is a core protein in biological and metabolic process of this pathogen. Moreover, this protein occurs in the thiamine thiazole biosynthesis pathway which is unique to F.solani and devoid in human. Hence, we predicted a plausible structure for this protein and also performed ligand-binding cavity analysis which can be for a strong base for drug designing studies. This study will pave way in better understanding of potential drug targets in F.solani and also leading to therapeutic interventions of fungal keratitis.
authors.affiliation: Centre for Bioinformatics, Vision Research Foundation, Chennai, India.
authors.forename: Muthukumaran
authors.initials: M
authors.lastname: Sivashanmugam
authors.affiliation: Rajalakshmi Engineering College, Thandalam, Chennai, India.
authors.forename: Hemavathy
authors.initials: H
authors.lastname: Nagarajan
authors.affiliation: Centre for Bioinformatics, Vision Research Foundation, Chennai, India. Electronic address: vumashankar@gmail.com.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Vetrivel
authors.affiliation: L&T Microbiology Research Centre, Vision Research Foundation, Chennai, India.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Ramasubban
authors.affiliation: L&T Microbiology Research Centre, Vision Research Foundation, Chennai, India.
authors.forename: Kulandai Lily
authors.initials: KL
authors.lastname: Therese
authors.affiliation: L&T Microbiology Research Centre, Vision Research Foundation, Chennai, India.
authors.forename: Madhavan Hajib
authors.initials: MH
authors.lastname: Narahari
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D015821:Eye Infections, Fungal / Q000382:microbiology*; D005656:Fungal Proteins / Q000378:metabolism*; D005670:Fusarium / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007194:India; D007634:Keratitis / Q000382:microbiology*; D040901:Proteomics / Q000379:methods; D013831:Thiamine / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D005656:Fungal Proteins; C057793:thiamine thiazolone; D013831:Thiamine