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

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.

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

“…Flavones are dual fused aromatic rings (A and C) with an extension of a benzene ring (B) at position 2 of ring C (Figure 3) [87]. The skeleton "ring A fused with ring C" has previously reported to possess antiviral activity against the dengue virus NS2B-NS3 complex [88]. Moreover, hydroxylation on ring A, particularly on positions 5 and 7, was found to be favorable for antiviral activity against the influenza A virus [89].…”

Evaluation of Flavonoids as 2019-nCoV Cell Entry Inhibitor Through Molecular Docking and Pharmacological Analysis

“…The present study emphasizes on the modeling of receptor binding domain (RBD) of nCoV-SP and generating a stable protein model which puts insight into its structure for possible interaction study of the protein with our choice of inhibitors and binds to the possible important residues of RBD that are crucial in interaction with the human receptor and further viral entry into the cell and pathogenesis. Flavonoids with its broad biological activity including antiviral activity against other viruses as well as SARS [33][34][35][36][37][38][39][40][41][42][43][44] were taken under consideration in this study, as molecular works of flavonoids against SARS-CoV and SARS-CoV-2 have not been done yet.…”

“…Different flavonoids with antioxidant, hepatoprotective, antibacterial, anti-inflammatory, anticancer and antiviral properties from different literatures were considered [15][16]. Flavonoids possessing antiviral activity against some viruses including coronavirus were also taken into consideration [33][34][35][36][37][38][39][40][41][42][43][44]. However, no study on the molecular level of flavonoids has been reported against nCoV-SP and, hence, flavonoids were considered in this computational study against For better reliability and precise results two docking software, PyRx [45] and iGEMDOCK [46] (N=800), 80 generation and 10 solutions were carried out with our choice of ligands in iGEMDOCK against both the protein models [47,48].…”

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

“…Hence, to overcome such situation presently, available more resources, much faster, and advance scientific techniques need to be adopted and explored. Earlier, a number of studies have proposed various traditional and specific methods for the identification of different chemical entities and demonstrated their selective inhibition mechanism and inhibitory efficacy against NS3‐NS2B protease complex at different levels …”