title: Homology modeling and virtual screening for antagonists of protease from yellow head virus.
abstract: Yellow head virus (YHV) is one of the causative agents of shrimp viral disease. The prevention of YHV infection in shrimp has been developed by various methods, but it is still insufficient to protect the mass mortality in shrimp. New approaches for the antiviral drug development for viral infection have been focused on the inhibition of several potent viral enzymes, and thus the YHV protease is one of the interesting targets for developing antiviral drugs according to the pivotal roles of the enzyme in an early stage of viral propagation. In this study, a theoretical modeling of the YHV protease was constructed based on the folds of several known crystal structures of other viral proteases, and was subsequently used as a target for virtual screening-molecular docking against approximately 1364 NCI structurally diversity compounds. A complex between the protease and the hit compounds was investigated for intermolecular interactions by molecular dynamics simulations. Five best predicted compounds (NSC122819, NSC345647, NSC319990, NSC50650, and NSC5069) were tested against bacterial expressed YHV. The NSC122819 showed the best inhibitory characteristic among the candidates, while others showed more than 50 % of inhibition in the assay condition. These compounds could potentially be inhibitors for curing YHV infection.
authors.affiliation: Department of Biochemistry, Faculty of Science, Kasetsart University, 50 Ngam Wong Wan Rd, Chatuchak, Bangkok, 10900, Thailand.
authors.forename: Sasimanas
authors.initials: S
authors.lastname: Unajak
authors.forename: Orathai
authors.initials: O
authors.lastname: Sawatdichaikul
authors.forename: Napat
authors.initials: N
authors.lastname: Songtawee
authors.forename: Siriluk
authors.initials: S
authors.lastname: Rattanabunyong
authors.forename: Anchalee
authors.initials: A
authors.lastname: Tassnakajon
authors.forename: Nontawith
authors.initials: N
authors.lastname: Areechon
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hirono
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kondo
authors.forename: Pongsak
authors.initials: P
authors.lastname: Khunrae
authors.forename: Triwit
authors.initials: T
authors.lastname: Rattanarojpong
authors.forename: Kiattawee
authors.initials: K
authors.lastname: Choowongkomon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D033561:Penaeidae / Q000821:virology; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D046828:Roniviridae / Q000201:enzymology* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D014764:Viral Proteins; D010447:Peptide Hydrolases