Poliovirus 3C proteinase inhibition by organotelluranes

Poliovirus 3C proteinase inhibition by organotelluranes

Author Gouvea, Iuri E. Autor UNIFESP Google Scholar
Santos, Jorge A. N. Autor UNIFESP Google Scholar
Burlandy, Fernanda M. Google Scholar
Tersariol, Ivarne L. S. Google Scholar
Silva, Edson E. da Google Scholar
Juliano, Maria A. Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Cunha, Rodrigo L. O. R. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Oswaldo Cruz
Univ Mogi das Cruzes
Universidade Federal do ABC (UFABC)
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 mM, 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.
Keywords antiviral
protease inhibitor
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2011-04-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 392, n. 6, p. 587-591, 2011.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 587-591
Origin http://dx.doi.org/10.1515/BC.2011.059
Access rights Closed access
Type Article
Web of Science ID WOS:000290715200010
URI http://repositorio.unifesp.br/handle/11600/33628

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