title: A 3D model of SARS_CoV 3CL proteinase and its inhibitors design by virtual screening.
abstract: OBJECTIVE
  To constructed a three-dimensional (3D) model for the 3C like (3CL) proteinase of SARS coronavirus (SARS-CoV), and to design inhibitors of the 3CL proteinase based on the 3D model.
  
  
  METHODS
  Bioinformatics analyses were performed to search the homologous proteins of the SARS-CoV 3CL proteinase from the GenBank and PDB database. A 3D model of the proteinase was constructed by using homology modeling technique. Targeting to the 3D model and its X-ray crystal structure of the main proteinase (Mpro) of transmissible gastroenteritis virus (TGEV), virtual screening was performed employing molecular docking method to identify possible 3CL proteinase inhibitors from small molecular databases.
  
  
  RESULTS
  Sequence alignment indicated that the SARS-CoV 3CL proteinase was extremely homologous to TGEV Mpro, especially the substrate-binding pocket (active site). Accordingly, a 3D model for the SARS-CoV 3CL proteinase was constructed based on the crystal structure of TGEV Mpro. The 3D model adopts a similar fold of the TGEV Mpro, its structure and binding pocket feature are almost as same as that of TGEV Mpro. The tested virtual screening indicated that 73 available proteinase inhibitors in the MDDR database might dock into both the binding pockets of the TGEV Mpro and the SARS-CoV 3CL proteinase.
  
  
  CONCLUSIONS
  Either the 3D model of the SARS-CoV 3CL proteinase or the X-ray crystal structure of the TGEV Mpro may be used as a starting point for design anti-SARS drugs. Screening the known proteinase inhibitors may be an appreciated shortcut to discover anti-SARS drugs.
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xiong
authors.forename: Chun-Shan
authors.initials: CS
authors.lastname: Gui
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Chen
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Chang-Ying
authors.initials: CY
authors.lastname: Yu
authors.forename: Li-Duo
authors.initials: LD
authors.lastname: Yue
authors.forename: Wen-Hu
authors.initials: WH
authors.lastname: Duan
authors.forename: Jing-Kang
authors.initials: JK
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.forename: Tie-Liu
authors.initials: TL
authors.lastname: Shi
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Li
authors.forename: Kai-Xian
authors.initials: KX
authors.lastname: Chen
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Luo
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Shen
authors.forename: Hua-Liang
authors.initials: HL
authors.lastname: Jiang
mesh_terms: D019295:Computational Biology; D000086782:Coronavirus 3C Proteases; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000302:isolation & purification*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D045169:Severe Acute Respiratory Syndrome / Q000821:virology*; D040681:Structural Homology, Protein; D005760:Transmissible gastroenteritis virus / Q000737:chemistry
chemical_list: D015853:Cysteine Proteinase Inhibitors; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases