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Title: The thiazolobenzimidazole TBZE-029 inhibits enterovirus replication by targeting a short region immediately downstream from motif C in the nonstructural protein 2C
Authors: De Palma, Armando ×
Heggermont, Ward
Lanke, Kjerstin
Coutard, Bruno
Bergmann, Mirko
Monforte, Anna-Maria
Canard, Bruno
De Clercq, Erik
Chimirri, Alba
Pürstinger, Gerhard
Rohayem, Jacques
Van Kuppeveld, Frank
Neyts, Johan #
Issue Date: May-2008
Publisher: American Society for Microbiology (ASM)
Series Title: Journal of Virology vol:82 issue:10 pages:4720-4730
Abstract: TBZE-029 [1-(2,6-difluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4-a]benzimidazole] is a novel selective inhibitor of the replication of several enteroviruses. We show that TBZE-029 exerts its antiviral activity through inhibition of viral RNA replication, without affecting polyprotein processing. To identify the viral target of TBZE-029, drug-resistant coxsackievirus B3 (CVB3) was selected. Genotyping of resistant clones lead to the identification of 3 amino acid mutations in the non-structural protein 2C, clustered at amino acid positions 224, 227 and 229 immediately downstream of the NTPase/helicase motif C. The mutations were reintroduced, either alone or combined, in an infectious full-length CVB3 clone. In particular the mutations at positions 227 and 229 proved essential for the altered sensitivity of CVB3 to TBZE-029. Resistant virus exhibited cross-resistance to the earlier reported anti-enterovirus agents targeting 2C, namely guanidine hydrochloride, HBB and MRL-1237. The ATPase activity of 2C, however, remained unaltered in the presence of TBZE-029.
ISSN: 0022-538X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Cardiology
× corresponding author
# (joint) last author

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