Enteroviruses are members of the picornavirus family, a large and diverse group of small RNA viruses. According to the present classification, the enterovirus genus comprises the following species: poliovirus, human enterovirus A (HEV-A) (coxackie A viruses and enterovirus 71), HEV-B (coxsackie B viruses, echoviruses, coxsackie A9 virus, and enteroviruses 69 and 73), HEV-C (coxsackie A viruses), HEV-D (enteroviruses 68 and 70), and at least three animal enterovirus species (bovine, simian, and porcine enteroviruses). They all contain a genome of approximately 7,500 bases and positive [(+)]-strand polarity. After infection of the host cell, the genome is translated in a cap-independent manner into a single polyprotein, which is subsequently processed by virus-encoded proteases into the structural capsid proteins and the nonstructural proteins, which are mainly involved in the replication of the virus.
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Pirlindole is a novel potent inhibitor of Enteroviruse that targets Viral Protein 2C, inhibits EV-B and EV-D through the inhibition of genome replication (CV-B3 EC50=9.91 uM).
ICA135 (ICA-135, ICA 135) is a broad-spectrum inhibitor against human enteroviruses that inhibits Coxsackievirus A10 (CV-A10) replication in RD cells with IC50 of 1.446 uM; exerts protective function in vivo in an established mouse model of CV-A10; exhibited inhibitory effect on Enteroviruses four species A-D with IC50 of 0.566 and 9.68 uM, including EV-A71 and CV-A16 from specie A, CV-B3 from specie B, PV-1 from specie C, and EV-D68 from specie D; bind to the VP1 hydrophobic pockets with high-binding affinity.
BF738735(BF 738735;BF-738735) is a novel, broad-spectrum inhibitor of enterovirus replication (EC50=4-71 nM) that specifically targets host cell factor PI4KIIIβ with IC50 of 5.7 nM, 300-fold less potent for PI4KIIIα (IC50=1.7 uM); blocks viral RNA replication with IC50 of 77 nM in luciferase assays, strongly inhibits CVB3 and EV71 replicon replication at 1-5 uM; reduces the PI4P levels at the Golgi complex through a direct inhibition of PI4KIIIβ activity.
SG85(SG 85) is a potent Enterovirus 3C protease inhibitor with EC50 of 180 nM against EV71 and 60 nM against human rhinovirus 14 in a live virus-cell-based assay; effectively inhibits the in vitro replication of 14 rhinoviruses representative of species A and B with mean EC50 of 40 nM, efficiently blocks rhinovirus replication and is not cross-resistant with rupintrivir.
TBZE-029(TBZE029) is a selective inhibitor of the replication of several Enteroviruses with IC50 of 1.2 uM against coxsackievirus B3 replication, targets nonstructural protein 2C.
MRL-1237(MRL1237) is a potent and selective inhibitor of the replication of Enteroviruses with EC50 of 1-10 uM, targets the nonstructural 2C protein; inhibits poliovirus-specific RNA synthesis in HeLa cells infected with a wild strain but not with an F164Y mutant.
TTP-8307(TTP8307) is a potent inhibitor of the replication of several Rhinoviruses and Enteroviruses, targets the nonstructural protein 3A, inhibits the replication of coxsackievirus B3 (CVB3 Nancy) with EC50 of 1.2 uM; 3A mutations V45A, I54F, and H57Y confer resistance to TTP-8307.
AN-12-H5 is a bifunctional, enviroxime-like anti-Enterovirus compound that inhibits replication and the early stage of enterovirus 71 infection with EC50 of 0.55 uM; mutations in capsid proteins (G3112A, VP1-Ala224Thr, and G2396A, VP3-Arg227Lys mutations) are resistant to AN-12-H5.
OSW-1 is a natural anti-enterovirus and anti-cancer compound that targets oxysterol-binding protein (OSBP) with Ki of 26 and 54 nM for OSBP and ORP4L, respectively; potently inhibits the replication of enteroviruses with IC50 values in the low nanomolar range; exhibits antiproliferative activity in HCT-116 and HeLa cell lines.
Vapendavir (BTA798) is a novel potent enteroviral capsid binder, inhibits EV71 replication of all isolates with mean EC50 of 0.7 uM; efficiently inhibits the in vitro replication of 21 EV71 strains/isolates that are representative of the different genogroups A, B, and C; Vapendavir (BTA798) is currently under clinical study for the treatment of rhinovirus infections.
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