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Title: Mutations in the non-structural protein 3A confer resistance to the novel enterovirus replication inhibitor TTP-8307
Authors: De Palma, Armando
Thibaut, Hendrik Jan
van der Linden, Lonneke
Lanke, Kjerstin
Heggermont, Ward
Ireland, Stephen
Andrews, Robert
Arimilli, Murty
Al-Tel, Taleb H
De Clercq, Erik
van Kuppeveld, Frank
Neyts, Johan # ×
Issue Date: May-2009
Publisher: American Society for Microbiology (ASM)
Series Title: Antimicrobial Agents and Chemotherapy vol:53 issue:5 pages:1850-1857
Abstract: A novel compound, TTP-8307, was identified as a potent inhibitor of the replication of several rhino- and enteroviruses. TTP-8307 inhibits viral RNA synthesis in a dose-dependent manner, without affecting polyprotein synthesis and/or processing. Drug-resistant variants of coxsackievirus B3 were all shown to carry at least one amino acid mutation in the nonstructural protein 3A. In particular, three mutations located in a nonstructured region preceding the hydrophobic domain (V45A, I54F, and H57Y) appeared to contribute to the drug-resistant phenotype. This region has previously been identified as a hot sport for mutations that resulted in resistance to enviroxime, the sole 3A-targeting enterovirus inhibitor reported thus far. This was corroborated by the fact that TTP-8307 and enviroxime proved cross-resistant. It is hypothesized that TTP-8307 and enviroxime disrupt proper interactions of 3A(B) with other viral or cellular proteins that are required for efficient replication.
URI: 
ISSN: 0066-4804
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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