title: Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.
abstract: BACKGROUND
  The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication.
  
  
  METHODS
  These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells.
  
  
  RESULTS
  Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cell-protective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC50) as low as 0.3 µM (Selectivity index or SI = 483), and selectivity indexes greater than 857 (EC50 = 0.6 µM) and 1524 (EC50 = 0.33 µM).
  
  
  CONCLUSIONS
  Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs.
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato (CA), Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Bernard
authors.affiliation: Department of Microbiology and Immunology, Laboratory for Virology and Chemotherapy, KU Leuven - University of Leuven, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Lacroix
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato (CA), Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Cabiddu
authors.affiliation: Department of Microbiology and Immunology, Laboratory for Virology and Chemotherapy, KU Leuven - University of Leuven, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Department of Microbiology and Immunology, Laboratory for Virology and Chemotherapy, KU Leuven - University of Leuven, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy rpompei@unica.it.
authors.forename: Raffaello
authors.initials: R
authors.lastname: Pompei
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004770:Enterovirus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010080:Oxazoles; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D010069:Oxadiazoles; D010080:Oxazoles; D010880:Piperidines; D011724:Pyridazines; C115201:pleconaril; C074589:pirodavir
keywords: Enterovirus; antivirals; early stage; pirodavir; pleconaril