Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease

Adeel Riaz,Muhammad Waseem Sarwar,Muhammad Mubin,Syed Muhammad Raihan Dilshad,Muhammad Shah Nawaz-Ul-Rehman,Ahmed Al-Qahtani

doi:10.1186/s12900-018-0084-5

Abstract

BackgroundDue to dengue virus disease, half of the world population is at severe health risk. Viral encoded NS2B-NS3 protease complex causes cleavage in the nonstructural region of the viral polyprotein. The cleavage is essentially required for fully functional viral protein. It has already been reported that if function of NS2B-NS3 complex is disrupted, viral replication is inhibited. Therefore, the NS2B-NS3 is a well-characterized target for designing antiviral drug.ResultsIn this study docking analysis was performed with active site of dengue NS2B-NS3 protein with selected plant flavonoids. More than 100 flavonoids were used for docking analysis. On the basis of docking results 10 flavonoids might be considered as the best inhibitors of NS2B-NS3 protein. The interaction studies showed resilient interactions between ligand and receptor atoms. Furthermore, QSAR and SAR studies were conducted on the basis of NS2B-NS3 protease complex docking results. The value of correlation coefficient (r) 0.95 shows that there was a good correlation between flavonoid structures and selected properties.ConclusionWe hereby suggest that plant flavonoids could be used as potent inhibitors of dengue NS2B-NS3 protein and can be used as antiviral agents against dengue virus. Out of more than hundred plant flavonoids, ten flavonoid structures are presented in this study. On the basis of best docking results, QSAR and SAR studies were performed. These flavonoids can directly work as anti-dengue drug or with little modifications in their structures.

Highlights

IntroductionViral encoded Non structural protein 2B (NS2B)-Non structural protein 3 (NS3) protease complex causes cleavage in the nonstructural region of the viral polyprotein
Due to dengue virus disease, half of the world population is at severe health risk
One common scaffold was obtained from the alignment of all ten flavonoid structures (Fig. 7). These results show that there is a prevalence of similarity among the structural formulas of different flavonoid compounds performing the same function i.e. binding with active site of Non structural protein 3 (NS3)-NSB protein of dengue virus

Summary

Introduction

Viral encoded NS2B-NS3 protease complex causes cleavage in the nonstructural region of the viral polyprotein. The cleavage is essentially required for fully functional viral protein. It has already been reported that if function of NS2B-NS3 complex is disrupted, viral replication is inhibited. Dengue virus belonging to family Flaviviridae is the most prevalent arthropod transmitted virus in humans. It can cause symptoms ranging from self-limiting dengue fever to sometimes-fatal dengue hemorrhagic fever [1]. NS3 protease requires the central hydrophilic region of NS2B (NS2B; residues 49 to 95) to perform proteolytic activity and to stabilize folding. Hydrophilic domain of NS2B interacts with NS3 protease and forms full active site [4]. The activity of Sarwar et al BMC Structural Biology (2018) 18:6 group Inc. and Chimera software was used for protein structure manipulation

Methods

Results

Discussion

Conclusion