TBZE-029 {1-(2,6-difluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4-a]benzimidazole} is a novel selec-Entero-and rhinoviruses are involved in a wide range of infections in humans and animals. Among the species in the enterovirus genus are the coxsackieviruses, which have been reported to be associated with various clinical manifestations, including myocarditis, pancreatitis, meningitis, and encephalitis. Other clinically relevant enteroviruses are poliovirus, which can cause paralytic poliomyelitis, and echovirus, causing aseptic meningitis or encephalomyelitis (33,36,43). Rhinoviruses are the main pathogens associated with the common cold, and, although usually mild and self-limiting, rhinovirus infections have an enormous socioeconomical impact (47,59).Enteroviruses belong to the family Picornaviridae, which consists of small, nonenveloped viruses containing a singlestranded positive-strand RNA [(ϩ)RNA] genome of 7.5 kb, which is covalently linked to a small viral protein (VPg) at its 5Ј end and polyadenylated at its 3Ј end (49). The genomic RNA has a long, highly structured 5Ј noncoding region, which contains the internal ribosome entry site, necessary for translation initiation, and a shorter 3Ј noncoding region preceding the poly(A) tract, which are both thought to be involved in RNA replication and translation (9). The coding region encodes a single polyprotein that will eventually be cleaved to generate 4 structural and 10 nonstructural proteins (either mature or in their precursor form). The icosahedral capsid of the virus is formed by 60 protomers, each one assembled by the four structural proteins, designated VP1 to -4. The nonstructural region comprises two proteases, the viral RNA-dependent RNA polymerase and seven other proteins that are involved in viral replication (8).One of the most conserved nonstructural viral proteins among picornaviruses is 2C. Although this protein is an indispensable component of the replication complex, its exact role in viral replication has remained elusive. Protein 2C appears to be multifunctional, and this entails multiple interactions (23). The amino acid sequence of 2C contains three conserved motifs which are typically found in NTP-binding proteins (motifs A and B) or in members of helicase superfamily III (motif C) (28)(29)(30)(31)69). In fact, ATPase activity has been demonstrated for several picornavirus 2C proteins (37, 57, 60) whereas so far, every attempt to demonstrate in vitro RNA helicase activity has failed. Protein 2C contains two regions involved in RNA binding (58). It has been suggested that, in poliovirus, this binding occurs at the 3Ј cloverleaf of (Ϫ)RNA (3-5); for echovirus, RNA binding was reported to occur in a nonspecific way