title: Design, virtual screening and docking study of novel NS3 inhibitors by targeting protein-protein interacting sites of dengue virus - a novel approach.
abstract: Currently dengue is a serious disease which has become a global burden in the last decade. Unfortunately, there are no effective drugs and vaccines against this disease. DENV non-structural protein (NS) 3, which is viral protease which is a potential target for antiviral therapy. Targeting this we performed homology modeling and protein-protein docking study of NS3 with NRBP (Nuclear Receptor Binding Protein) of human as it has been proved that NS3 of DENV interacts with NRBP which causes cellular trafficking in human cell. To carry out search of novel DENV protease inhibitors by in silico screening panduratin molecule was selected. 65 novel compounds were designed which involved substituting positions 1-5 of the benzyl ring A (4hydroxy-panduratinA) with various substituents. The protein-protein docking showed that the aminoacid residues of NS3 which were interacting with NRBP were found to be Ala 325, Asp 324, Phe 326, Asp 335, Glu 336, Glu 328, Asp 485, Gln 478, Arg 459, Gly 446 and Leu 480. These residues were targeted by the ligands which showed excellent binding affinity as binding energy. The ligand PKP10 showed lowest binding energy. It is also observed that the interface residues participated in the protein-protein interaction are being inhibited by the ligands.
authors.forename: Pratap
authors.initials: P
authors.lastname: Parida
authors.forename: R N S
authors.initials: RN
authors.lastname: Yadav
authors.forename: Kishore
authors.initials: K
authors.lastname: Sarma
authors.affiliation: Centre for Studies in Biotechnology, Dibrugarh University, Assam-786004, India. pratapparida2007yahoo.com@gmail.com.
authors.forename: Lalit Mohan
authors.initials: LM
authors.lastname: Nainwal
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D062105:Molecular Docking Simulation / Q000379:methods*; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D020365:RNA Helicases / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry; D014584:User-Computer Interface; D033921:Vesicular Transport Proteins / Q000737:chemistry*; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D011480:Protease Inhibitors; D020365:RNA Helicases; D018160:Receptors, Cytoplasmic and Nuclear; D012697:Serine Endopeptidases; D033921:Vesicular Transport Proteins; D017361:Viral Nonstructural Proteins; C410809:NRBP1 protein, human; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases