Discovery of potential Zika virus RNA polymerase inhibitors by docking-based virtual screening. (December 2017)

• Record Type: Journal Article
• Authors: Singh, Anjali; Jana, Nandan Kumar
• Is Part Of: Computational biology and chemistry. Volume 71(2017)
• Page Start: 144
• Page End: 151
• Publication Date: 2017-12
• Subjects: Zika virus -- Docking -- Virtual screening -- RNA polymerase -- Inhibitors; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2017.10.007
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Virtual screening and docking studies for discovering potential inhibitors against catalytic region of Zika virus RNA dependent RNA polymerase (RdRpC). Highlights: We attempted to model the catalytic domain of Zika virus RNA polymerase (ZIKV RdRpC). Identification of important conserved aspartates in ZIKV RdRpC palm domain as potential drug targets. A virtual screening of ZIKV RdRpC inhibitors was performed. Abstract: Zika virus (ZIKV) infection has been associated with Guillain-Barre syndrome in adults and microcephaly in infants. The existence of insufficient structural data in most of the protein databases hinders the synthesis of anti-ZIKV pharmaceutics. In this work, we attempted to model the catalytic domain of the ZIKV RNA polymerase (RdRpC) along with a detailed assessment of conserved aspartates in ZIKV RdRpC palm domain as potential drug targets. The conserved and catalytically active aspartate residues present in the predicted RdRpC protein were virtually screened against a ZINC database for inhibitors, and the selected potential drug candidates were further filtered based on their ADMET profiles. One of the pharmacokinetically active compounds (Ligand 6) showed a remarkable docking profile against the strictly conserved aspartate residues of the RdRpC active site. We hypothesize that the Ligand 6 may form a potential drug candidate for RdRpC inhibition in the clinical treatment of ZIKV infection.