Antiviral activity of acid beta-glucosidase 1 on enterovirus 71, a causative agent of hand, foot and mouth disease

Nakata, Kohei; Takeda, Satoshi; Tanaka, Atsushi; Kwang, Jimmy; Komano, Jun

doi:10.1099/jgv.0.000723

Cited by 6 publications

(4 citation statements)

References 29 publications

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“…Previous in vitro studies demonstrated that hSCARB2 binds β-GC at pH 6.5, whereas it does not at pH 5.5 ( Zhao et al, 2014 ). Interestingly, the binding site(s) of hSCARB2 for β-GC [amino acids 145-222 ( Zachos et al, 2012 ) or 150–167 ( Reczek et al, 2007 )] overlaps with the binding site(s) for EV71 [amino acids 142-204 ( Yamayoshi and Koike, 2011 ) or 144–151 ( Chen et al, 2012 )], and exogenous β-GC has been found to interfere with EV71 binding to hSCARB2 on the cell surface ( Nakata et al, 2017 ). This implies that release of β-GC from hSCARB2 at pH 5.5 may enhance the interaction between EV71 and hSCARB2, thus boosting EV71 uncoating.…”

Section: Discussionmentioning

confidence: 99%

The uncoating of EV71 in mature late endosomes requires CD-M6PR

et al. 2022

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Enterovirus 71 (EV71) is one of the causative agents of hand-foot-and-mouth disease, which in some circumstances could lead to severe neurological diseases. Despite of its importance for human health, little is known about the early stages of EV71 infection. EV71 starts uncoating with its receptor, human scavenger receptor B2 (hSCARB2), at low pH. We show that EV71 was not targeted to lysosomes in human rhabdomyosarcoma cells overexpressing hSCARB2 and that the autophagic pathway is not essential for EV71 productive uncoating. Instead, EV71 was efficiently uncoated 30 minutes after infection in late endosomes (LEs) containing hSCARB2, mannose-6-phosphate receptor (M6PR), RAB9, bis(monoacylglycero)phosphate and lysosomal associated membrane protein 2 (LAMP2). Furthering the notion that mature LEs are crucial for EV71 uncoating, cation-dependent (CD)-M6PR knockdown impairs EV71 infection. Since hSCARB2 interacts with cation-independent (CI)-M6PR through M6P-binding sites and CD-M6PR also harbor a M6P-binding site, CD-M6PR is likely to play important roles in EV71 uncoating in LEs.

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Section: Discussionmentioning

confidence: 99%

The uncoating of EV71 in mature late endosomes requires CD-M6PR

et al. 2022

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“…EV71 infection is strongly associated with severe HFMD, which is accompanied by neurological symptoms and usually leads to death. Therefore, many studies have focused on the identification of substances with activity against EV71, and these studies have identified many candidate drugs for the treatment of EV71 infection, such as amphotericin B, isochlorogenic acid C, acid beta‐glucosidase 1, sulfated rhamnan, and suramin . Considering their relatively low cytotoxicity, extracts from traditional Chinese medicines or foods show particular advantages and have attracted increasing attention …”

Section: Discussionmentioning

confidence: 99%

Virucidal activity and the antiviral mechanism of acidic polysaccharides against Enterovirus 71 infectionin vitro

Cui

Liu

et al. 2020

Microbiology and Immunology

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Enterovirus 71 (EV71) is the predominant pathogen for severe hand, foot, and mouth disease (HFMD) in children younger than 5 years, and currently no effective drugs are available for EV71. Thus, there is an urgent need to develop new drugs for the control of EV71 infection. In this study, LJ04 was extracted from Laminaria japonica using diethylaminoethyl cellulose‐52 with 0.4 mol/l NaCl as the eluent, and its virucidal activity was evaluated based on its cytopathic effects on a microplate. LJ04 is composed of fucose, galactose, and mannose and mainly showed good virucidal activity against EV71. The antiviral mechanisms of LJ04 were the direct inactivation of the virus, the blockage of virus binding, disruptions to viral entry, and weak inhibitory activity against the nonstructural protein 3C. The two most important findings from this study were that LJ04 inhibited EV71 proliferation in HM1900 cells, which are a human microglia cell line, and that LJ04 can directly inactivate EV71 within 2 hr at 37°C. This study demonstrates for the first time the ability of a polysaccharide from L. japonica to inhibit viral and 3C activity; importantly, the inhibition of 3C might have a minor effect on the antiviral effect of LJ04. Consequently, our results identify LJ04 as a potential drug candidate for the control of severe EV71 infection in clinical settings.

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“…For instance, SCARB2 was identified as a receptor for EV71 by Yamayoshi et al [50]. Nakata et al [51] later reported that acid beta-glucosidase 1 (GAB1) restricts EV71 infections by interacting with SCARB2 and reducing its expression on the cell surface. Further, it was shown that recombinant human GBA1, a drug originally used to treat Gaucher's disease, protected against EV71 infection [2].…”

Section: Newer Approachesmentioning

confidence: 99%

Update on nonpolio enterovirus and parechovirus infections in neonates and young infants

Souverbielle

Erdem

Sánchez

2023

Current Opinion in Pediatrics

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Purpose of reviewTo review the epidemiology, clinical manifestations, and treatment strategies of nonpolio enterovirus and parechovirus (PeV) infections, and identify research gaps. Recent findingsThere is currently no approved antiviral agent for enterovirus or PeV infections, although pocapavir may be provided on a compassionate basis. Elucidation of the structure and functional features of enterovirus and PeV may lead to novel therapeutic strategies, including vaccine development. SummaryNonpolio human enterovirus and PeV are common childhood infections that are most severe among neonates and young infants. Although most infections are asymptomatic, severe disease resulting in substantial morbidity and mortality occurs worldwide and has been associated with local outbreaks. Longterm sequelae are not well understood but have been reported following neonatal infection of the central nervous system. The lack of antiviral treatment and effective vaccines highlight important knowledge gaps. Active surveillance ultimately may inform preventive strategies.

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Antiviral activity of acid beta-glucosidase 1 on enterovirus 71, a causative agent of hand, foot and mouth disease

Cited by 6 publications

References 29 publications

The uncoating of EV71 in mature late endosomes requires CD-M6PR

The uncoating of EV71 in mature late endosomes requires CD-M6PR

Virucidal activity and the antiviral mechanism of acidic polysaccharides against Enterovirus 71 infectionin vitro

Update on nonpolio enterovirus and parechovirus infections in neonates and young infants

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