Angela Bernard1, Céline Lacroix2, Maria G Cabiddu1, Johan Neyts2, Pieter Leyssen2, Raffaello Pompei3. 1. Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato (CA), Italy. 2. Department of Microbiology and Immunology, Laboratory for Virology and Chemotherapy, KU Leuven - University of Leuven, Rega Institute for Medical Research, Leuven, Belgium. 3. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy rpompei@unica.it.
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). CONCLUSION: 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.
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). CONCLUSION: 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: Els Wessels; Daniël Duijsings; Richard A Notebaart; Willem J G Melchers; Frank J M van Kuppeveld Journal: J Virol Date: 2005-04 Impact factor: 5.103
Authors: F G Hayden; G J Hipskind; D H Woerner; G F Eisen; M Janssens; P A Janssen; K Andries Journal: Antimicrob Agents Chemother Date: 1995-02 Impact factor: 5.191
Authors: Tom Solomon; Penny Lewthwaite; David Perera; Mary Jane Cardosa; Peter McMinn; Mong How Ooi Journal: Lancet Infect Dis Date: 2010-10-18 Impact factor: 25.071
Authors: Ville Peltola; Matti Waris; Riikka Osterback; Petri Susi; Timo Hyypiä; Olli Ruuskanen Journal: J Clin Virol Date: 2008-10-02 Impact factor: 3.168
Authors: Patrick Mallia; Simon D Message; Vera Gielen; Marco Contoli; Katrina Gray; Tatiana Kebadze; Julia Aniscenko; Vasile Laza-Stanca; Michael R Edwards; Louise Slater; Alberto Papi; Luminita A Stanciu; Onn M Kon; Malcolm Johnson; Sebastian L Johnston Journal: Am J Respir Crit Care Med Date: 2010-10-01 Impact factor: 21.405
Authors: Frederick G Hayden; Darrell T Herrington; Teresa L Coats; Kenneth Kim; Ellen C Cooper; Stephen A Villano; Siyu Liu; Spencer Hudson; Daniel C Pevear; Marc Collett; Mark McKinlay Journal: Clin Infect Dis Date: 2003-06-06 Impact factor: 9.079