Progress in targeted delivery of siRNA to combat Coxsackievirus

Gautam, Anju

doi:10.1007/s13238-011-1124-0

Cited by 5 publications

(2 citation statements)

References 20 publications

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“…In particular, young children and the population with immunodeficiency are more susceptible to EV71 infection. The infection causes severe aseptic meningitis, encephalitis, myocarditis, acute flaccid paralysis, and pulmonary edema, which lead to high fatality rates (Zhang et al, 2010;Cui et al, 2010;Yang et al, 2009;Gautam, 2011;Sun et al, 2012;Zhou et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation

et al. 2014

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Section: Introductionmentioning

confidence: 99%

An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation

et al. 2014

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“…These agents caused over 1,000,000 infections and 900 deaths in 2010 (China Ministry of Health, http://www.moh.gov.cn/publicfiles /business/htmlfiles/mohjbyfkzj/s3578/201102/50646.htm). In particular, young children are more susceptible to infection with EV71 (3,4), which causes severe aseptic meningitis, encephalitis, myocarditis, acute flaccid paralysis, and pulmonary edema, which lead to high fatality rates (2,(5)(6)(7).…”

mentioning

confidence: 99%

Crystal Structure of Enterovirus 71 RNA-Dependent RNA Polymerase Complexed with Its Protein Primer VPg: Implication for a trans Mechanism of VPg Uridylylation

Chen

Wang

Shan

et al. 2013

J Virol

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g Picornavirus RNA replication is initiated by VPg uridylylation, during which the hydroxyl group of the third tyrosine residue of the virally encoded protein VPg is covalently linked to two UMP molecules by RNA-dependent RNA polymerase (RdRp; also known as 3D pol ). We previously identified site 311, located at the base of the palm domain of the enterovirus 71 (EV71) RdRp, to be the site for EV71 VPg binding and uridylylation. Here we report the crystal structure of EV71 3D pol complexed with VPg. VPg was anchored at the bottom of the palm domain of the 3D pol molecule and exhibited an extended V-shape conformation. The corresponding interface on 3D pol was mainly formed by residues within site 311 and other residues in the palm and finger domains. Mutations of the amino acids of 3D pol involved in the VPg interaction ( 3D L319A, 3D D320A, and 3D Y335A) significantly disrupted VPg binding to 3D pol , resulting in defective VPg uridylylation. In contrast, these mutations did not affect the RNA elongation activity of 3D pol . In the context of viral genomic RNA, mutations that abolished VPg uridylylation activity were lethal for EV71 replication. Further in vitro analysis showed that the uridylylation activity was restored by mixing VPg-binding-defective and catalysis-defective mutants, indicating a trans mechanism for EV71 VPg uridylylation. Our results, together with previous results of other studies, demonstrate that different picornaviruses use distinct binding sites for VPg uridylylation. Picornaviridae members make up one of the largest family of viruses and cause a wide range of infectious diseases in plants, animals, and humans. As the members of Picornaviridae, enterovirus 71 (EV71) and coxsackievirus (CV) are the major causative agents of hand, foot, and mouth disease (HFMD) in mainland China (1, 2). These agents caused over 1,000,000 infections and 900 deaths in 2010

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