Antiviral activity of hexapeptides derived from conserved regions of bacterial proteases against HCV NS3 protease

Abstract

The main cause of hepatitis C is hepatitis C virus or HCV and for the cure of hepatitis C, NS3/4A protease has been found an important and emerging target. A number of HCV NS3/4A protease inhibitors have been discovered which have shown subsequent reduction in reducing the viral load leading to this infection however they are still undergoing clinical trials for improvement. Bacterial proteases are of great pharmaceutical importance and have a key role in various biological processes and in life cycle of several pathogens. The current study was planned to explore hexapeptides derived from conserved regions of bacterial proteases for their potential in blocking the NS3 protease activity of HCV which would finally inhibit HCV multiplication. For this, a novel protease gene nprB was isolated from a thermophilic bacterium Streptomyces thermovulgaris and bioinformatics analyses were performed. PCR amplification and sequencing of nprB gene indicated an open reading frame of 178 aa (20191.18 Dalton).The peptide GGVHIN was the top ranked with minimum S-score of -17.21) followed by hexapeptides VDAHAN, GVGREA, GALNES and VHINSS with their S-scores of -14.73, -13.78, -10.72 and -10.70, respectively. A phylogram was also reconstructed to reveal evolutionary relationships of nprB with its various homologs. The provided data will serve as a background to further reveal pharmaceutical and biotechnological importance of this novel protease gene from S. thermovulgaris in future.