title: Poliovirus 3C proteinase inhibition by organotelluranes.
abstract: The 3C proteinase, essential for human poliovirus (PV) replication, has unique characteristics as its three-dimensional structure resembles chymotrypsin, but its catalytic nucleophile is a cysteine SH group rather than the OH group of serine. Here, we describe the use of tellurium compounds as inhibitors of PV3C proteinase. A rapid, stoichiometric and covalent inactivation of PV3C was observed with both a chloro-telluroxetane and a bis-vinylic organotellurane. These compounds also inhibit human cathepsins B, L, S, and K with second order rate constants higher than those obtained for PV3C. Chloro-telluroxetane inhibits replication of PV in human embryonic rhabdomyosarcoma cells in the low micromolar range and below the toxic level for the host cells. Bis-vinylic organotellurane is more effective as antiviral agent but reduces the cell viability by 20% at 10 μm, a concentration almost completely inhibiting virus growth. This is the first description of inhibition of viral 3C proteinase with antiviral property by this class of compounds.
authors.affiliation: Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio,100, São Paulo, SP 04044-020, Brazil.
authors.forename: Iuri E
authors.initials: IE
authors.lastname: Gouvea
authors.forename: Jorge A N
authors.initials: JA
authors.lastname: Santos
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Burlandy
authors.forename: Ivarne L S
authors.initials: IL
authors.lastname: Tersariol
authors.forename: Edson E
authors.initials: EE
authors.lastname: da Silva
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.forename: Rodrigo L O R
authors.initials: RL
authors.lastname: Cunha
mesh_terms: D000086042:3C Viral Proteases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D017955:Poliovirus / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013691:Tellurium / Q000737:chemistry*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D013691:Tellurium