Genetic and antigenic structural characterization for resistance of echovirus 11 to pleconaril in an immunocompromised patient

Benschop, Kimberley; Wildenbeest, Joanne G; Koen, Gerrit; Minnaar, R. P.; Hemert, Formijn J. van; Westerhuis, Brenda M.; Broek, P.J. van den; Vossen, Ann C.T.M.; Wolthers, Katja C.

doi:10.1099/vir.0.069773-0

Cited by 13 publications

(14 citation statements)

References 32 publications

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“…Indeed, in a clinical trial for the treatment of rhinovirus infections with pleconaril, compound-resistant viruses were isolated [7]. In addition, naturally occurring pleconaril-resistant viruses (e.g., an echovirus 11 strain) have been reported [8]. These resistance issues may complicate the application of capsid binders in the clinic.…”

Section: Direct-acting Antivirals Entry Inhibitorsmentioning

confidence: 99%

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Bauer

Lyoo

Schaar

et al. 2017

Current Opinion in Virology

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Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs.

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Section: Direct-acting Antivirals Entry Inhibitorsmentioning

confidence: 99%

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Bauer

Lyoo

Schaar

et al. 2017

Current Opinion in Virology

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“…Substitutions of amino acids in the center of the pocket that confer high-level resistance have also been reported for rhinoviruses Heinz et al, 1989;Ledford et al, 2005;Ledford et al, 2004;Zhang et al, 2004) and echovirus 11 (Benschop et al, 2015). The activity of pleconaril derivatives lacking one or both of the methyl groups of the central phenyl ring of pleconaril (Schmidtke et al, 2009) is less affected by the substitution of I1092.…”

Section: Discussionmentioning

confidence: 84%

“…I1092 is situated in the center of the pocket and interacts with one of the two methyl groups of pleconaril's phenyl ring. Substitutions of amino acids in the center of the pocket that confer high-level resistance have also been reported for rhinoviruses Heinz et al, 1989;Ledford et al, 2005;Ledford et al, 2004;Zhang et al, 2004) Ledford et al, 2005;Ledford et al, 2004;Zhang et al, 2004) and echovirus 11 (Benschop et al, 2015) (Benschop et al, 2015). The activity of pleconaril derivatives lacking one or both of the methyl groups of the central phenyl ring of pleconaril (Schmidtke et al, 2009) (Schmidtke et al, 2009) is less affected by the substitution of I1092.…”

Section: Discussionmentioning

confidence: 85%

“…All high-level resistance (HR) ) to CIs reported to date involve residues forming the hydrophobic pocket of EVEVs Benschop et al, 2015;Groarke and Pevear, 1999;Ledford et al, 2005;Ledford et al, 2004;Schmidtke et al, 2005) Benschop et al, 2015;Groarke and Pevear, 1999;Ledford et al, 2005;Ledford et al, 2004;Schmidtke et al, 2005), hence directly interfering with the binding of CIs. Because of similarities in the binding mode of CIs, cross-resistance may be observed, as reported for pleconaril and vapendavir (Feil et al, 2012) (Feil et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…All high-level resistance to CIs reported to date involve residues forming the hydrophobic pocket of EVs Benschop et al, 2015;Groarke and Pevear, 1999;Ledford et al, 2005;Ledford et al, 2004;Schmidtke et al, 2005), hence directly interfering with the binding of CIs. Because 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 of similarities in the binding mode of CIs, cross-resistance may be observed, as reported for pleconaril and vapendavir (Feil et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular mechanism of a specific capsid binder resistance caused by mutations outside the binding pocket

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Molecular characterization of a new human echovirus 11 isolate associated with severe hand, foot and mouth disease in Yunnan, China, in 2010

Zhou

Zhu

et al. 2015

Arch Virol

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Human echovirus 11 (E-11), a member of the species Enterovirus B, frequently causes aseptic meningitis and hand, foot and mouth disease (HFMD). We determined the complete genome sequence of strain 520K/YN/CHN/2010, isolated from a subject with HFMD and aseptic meningitis in Yunnan Province, China, in 2010. The strain shared 78.8% and 81.1% nucleotide sequence similarity with prototype strain Gregory in the complete VP1 gene and the complete genome, respectively. Only the VP2-VP3-VP1 genome region of 520K/YN/CHN/2010 was similar to that of the E-11 strain; the other genome regions were most similar to those of other members of the species Enterovirus B. Using phylogenetic analysis and sequence comparisons of the complete VP1 gene, E-11 strains could be divided into five genogroups, and the 520K/YN/CHN/2010 strain was found to belong to genogroup A. Recombination analysis showed evidence of recombination with other member of the species Enterovirus B, especially the E-9 strain MSH/KM812/2010. Persistent surveillance of HFMD pathogens might help predict potential emerging viruses and related disease outbreaks.

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Genetic and antigenic structural characterization for resistance of echovirus 11 to pleconaril in an immunocompromised patient

Cited by 13 publications

References 32 publications

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Molecular mechanism of a specific capsid binder resistance caused by mutations outside the binding pocket

Molecular characterization of a new human echovirus 11 isolate associated with severe hand, foot and mouth disease in Yunnan, China, in 2010

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