@article{fdi:010053453,
  title = {{P}icornavirus non-structural proteins as targets for new anti-virals with broad activity},
  author = {{N}order, {H}. and {D}e {P}alma, {A}.{M}. and {S}elisko, {B}. and {C}ostenaro, {L}. and {P}apageorgiou, {N}. and {A}rnan, {C}. and {C}outard, {B}. and {L}antez, {V}. and {L}amballerie, {X}avier de and {B}aronti, {C}{\'e}cile and {S}ola, {M}. and {T}an, {J}. and {N}eyts, {J}. and {C}anard, {B}. and {C}oll, {M}. and {G}orbalenya, {A}. {E}. and {H}ilgenfeld, {R}.},
  editor = {},
  language = {{ENG}},
  abstract = {{P}icornaviridae is one of the largest viral families and is composed of 14 genera, six of which include human pathogens. {T}he best known picornaviruses are enteroviruses (including polio, {PV}, and rhinoviruses), foot-and-mouth disease virus ({FMDV}), and hepatitis {A} virus ({HAV}). {A}lthough infections often are mild, certain strains may cause pandemic outbreaks accompanied with meningitis and/or paralysis. {V}accines are available for {PV}. {HAV} and {FMDV}. {W}hen the oral vaccines are given to immunocompromised individuals, they may be chronically infected, and remain secretors of vaccine-derived variants of virus for years. {T}here is no effective prophylaxis available for these or other picornaviruses. {S}o far, only the 3{C} protease from viruses in three genera has been fully characterized as an anti-viral target, whereas the mode of action of compounds targeting other non-structural proteins have remained largely unaddressed. {W}ithin the {EU}-supported {FP}6 project-{VIZIER} ({C}omparative {S}tructural {G}enomics of {V}iral {E}nzymes {I}nvolved in {R}eplication), the non-structural proteins were studied to identify conserved binding sites for broadly reactive anti-vitals. {T}he putative 2{C} helicase from echovirus-30 was shown to form ring-shaped hexamers typical for {DNA}-encoded {SF}3 helicases, and to possess {ATP}ase activity. {H}examer formation of 2{C} from enterovirus 76 was in vitro shown to be dependent on the 44 {N}-terminal residues. {C}rystal structures of three enterovirus 3{C} proteases were solved and shown to be similar to those of other picornaviruses. {A} new binding site of {VP}g to the bottom of the thumb domain of {CV}-{B}3 3{D} polymerase was identified as a potential target. {B}road anti-enterovirus compounds against 2{C} and 3{A} proteins were also identified, including thiazolobenzimidazoles (active against 2{C}) and {TTP}-8307 (targeting 3{A}). {T}here is a need for more potent inhibitors against {PV} and other picornavinises, which are potential silent reservoirs for re-emerging {PV}-like disease.},
  keywords = {{P}icornavirus ; {N}on-structural proteins ; {A}nti-viral compounds ; {E}nterovirus ; {P}olio ; {S}tructure},
  booktitle = {},
  journal = {{A}ntiviral {R}esearch},
  volume = {89},
  numero = {3},
  pages = {204--218},
  ISSN = {0166-3542},
  year = {2011},
  DOI = {10.1016/j.antiviral.2010.12.007},
  URL = {https://www.documentation.ird.fr/hor/fdi:010053453},
}