In silico screening of tripeptide inhibitors reveals potential lead compounds for targeting zika virus NS2B-NS3 protease

ZIKV is a public health threat causing neurological complications such as microcephaly and Guillain-Barre syndrome, with the additional risk of sexual transmission. The absence of FDA-approved drugs or vaccines for ZIKV, highlight the immediate requirement for potential therapeutics. A potential target for antiviral drug development is the NS2B-NS3 protease which is a critical enzyme in the replication and maturation of ZIKV. Here, we report the inhibitory activity of tripeptide compounds for this protease via molecular docking and molecular dynamics (MD) study. The docking studies were further followed by a 200 ns MD simulation to investigate the stability and binding mode of the inhibitor within the active site of protease. The simulation revealed that, the complex remains stable with lower root mean square deviation RMSD and higher root mean square fluctuation (RMSF) values and showed strong ligand-protein interaction. Further investigation of torsion angles in the ligand and secondary structural changes in the protease support to the viability of these tripeptide inhibitors as anti-viral agents. The results obtained in this study suggest that tripeptide-derived inhibitors of ZIKV may be applied as potential leads for developing novel therapies against the ZIKV, indicating a potential direction for future drug discovery and clinical treatments.