Open AccessThe Capsid Binder Vapendavir and the Novel Protease Inhibitor SG85 Inhibit Enterovirus 71 Replication
Author(s) -
Aloys Tijsma,
David Franco,
Simon Tucker,
Rolf Hilgenfeld,
Matheus Froeyen,
Pieter Leyssen,
Johan Neyts
Publication year - 2014
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.03328-14
Subject(s) - capsid , enterovirus 71 , in silico , virology , viral replication , enterovirus , poliovirus , protease , docking (animal) , in vitro , chemistry , virus , biology , protease inhibitor (pharmacology) , enzyme , biochemistry , viral load , gene , medicine , antiretroviral therapy , nursing
Antivirals against enterovirus 71 (EV71) are urgently needed. We demonstrate that the novel enteroviral protease inhibitor (PI) SG85 and capsid binder (CB) vapendavir efficiently inhibit the in vitro replication of 21 EV71 strains/isolates that are representative of the different genogroups A, B, and C. The PI rupintrivir, the CB pirodavir, and the host-targeting compound enviroxime, which were included as reference compounds, also inhibited the replication of all isolates. Remarkably, the CB compound pleconaril was devoid of any anti-EV71 activity. An in silico docking study revealed that pleconaril-unlike vapendavir and pirodavir-lacks essential binding interactions with the viral capsid. Vapendavir and SG85 (or analogues) should be further explored for the treatment of EV71 infections. The data presented here may serve as a reference when developing yet-novel inhibitors.
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