Structural Modeling of the NS 3 helicase of Tick-borne encephalitis virus and their virtual screening of potent drugs using molecular docking

Abstract

Homology modeling of NS3 helicase in Tick-borne encephalitis virus using known protein crystal structure was done. Its 3-D structure was evaluated and validated using PROCHECK comprising amino acid residues in favored region of Ramachandran plot. Helicase forms a large family of proteins which ubiquitously distributes in wide variety of organisms. It plays crucial role in transcription and replication of single-stranded viral RNA genomes. Consequently, NS3 represents an interesting target for the development of specific antiviral inhibitors. Several helicase inhibiting effective drugs and analogs were selected and the active amino acid residues were targeted. Levovirin, Ribamidine and Ribavirin were found more potent to inhibit TBEV on the basis of robust binding affinity between protein-drug interactions. This finding may help to understand the nature of helicase and development of specific anti-TBEV therapies.

Inhibition of tick-borne encephalitis virus in cell cultures by ribavirin

“…These results demonstrated that ribavirin could strongly inhibit TBEV propagation in the susceptible cells at a non-cytotoxic dose range. In agreement with our results, on the basis of protein-drug interactions, ribavirin potently inhibited TBEV by targeting TBEV NS3 helicase ( Singh and Somvanshi, 2009 ). Ribavirin significantly inhibited the proliferation of the highly virulent strain of the TBEV in the PK cell cultures ( Krylova and Leonova, 2016 ).…”

Gene Cloning and Homology Modeling of the 3-Oxoacyl-ACP Synthase from Aeromonas hydrophila for Drug Discovery

“…The 3-D structure of 3-oxoacyl-acyl carrier protein synthase II contributed in the synthesis of fatty acid which is essential for cell growth and viability of M. tuberculosis using homology modeling [27]. The homology modeling of NS3 helicase in Tick-borne encephalitis virus using known protein crystal structure has been reported for the development of specific anti-TBEV therapies [28]. The two-component bacterial systems involve sensor histidine kinase (SHK) and its response regulators are considered as a lucrative target for drug design.…”