title: Virtual Screening for Potential Inhibitors of NS3 Protein of Zika Virus.
abstract: Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Maheswata
authors.initials: M
authors.lastname: Sahoo
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Lingaraja
authors.initials: L
authors.lastname: Jena
authors.affiliation: Obstetrics & Gynaecology, Datta Meghe Institute of Medical Sciences (Deemed University), Nagpur 440-022, India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Daf
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
keywords: NS3 protein; drug design; flavivirus; high throughput screening methods; zika virus