Picornavirus non-structural proteins as targets for new anti-virals with broad activity

Nordér, Helené; Palma, Armando M. De; Selisko, Barbara; Costenaro, Lionel; Papageorgiou, Nicolas; Arnan, Carme; Coutard, Bruno; Lantez, Violaine; Lamballerie, Xavier De; Baronti, Cécile; Solà, Marı́a; Tan, Jingjing; Neyts, Johan; Canard, Bruno; Coll, Miquel; Gorbalenya, Alexander E.; Hilgenfeld, Rolf

doi:10.1016/j.antiviral.2010.12.007

Cited by 76 publications

(71 citation statements)

References 149 publications

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“…The DHAV proliferation process included virus adsorption, RNA replication, and virus release. 26 Regarding the process of virus adsorption, the relative DHAV gene expressions in the APS and sAPS groups revealed that these polysaccharides were unable to inhibit viral adsorption. At the 12th h, which represents the process of viral replication (Figure 3(b)), the relative DHAV gene expressions of the pAPS group were lower than those of the VC group, APS group, and sAPS group, and there were notably differences compared with the sAPS group and VC group (P < 0.05).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides

Wang

Chen

Yang

et al. 2016

Exp Biol Med (Maywood)

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Duck hepatitis A virus (DHAV) (Picornaviridae) causes an infectious disease in ducks which results in severe losses in duck industry. However, the proper antiviral supportive drugs for this disease have not been discovered. Polysaccharide is the main ingredient of Astragalus that has been demonstrated to directly and indirectly inhibit RNA of viruses replication. In this study, the antiviral activities of Astragalus polysaccharide (APS) and its derivatives against DHAV were evaluated and compared. APS was modified via the sodium trimetaphosphate and sodium tripolyphosphate (STMP-STPP) method and chlorosulfonic acid-pyridine method to obtain its phosphate (pAPS) and sulfate (sAPS), respectively. The infrared structures of APS, pAPS, and sAPS were analyzed with the potassium bromide disc method. Additionally, the antiviral activities were evaluated with the MTT ((4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method in vitro and the artificial inoculation method in vivo. The clinical therapy effects were evaluated by mortality rate, liver function-related biochemical indicators, and visual changes in pathological anatomy. The anti-DHAV proliferation effects of APS, pAPS, and sAPS on the viral multiplication process in cell and blood were observed with the reverse transcription-polymerase chain reaction method. The results revealed that pAPS inhibited DHAV proliferation more efficiently in the entire process of viral multiplication than APS and sAPS. Moreover, only pAPS significantly improved the survival rate to 33.5% and reduced the DHAV particle titer in the blood as well as liver lesions in clinical trials. The results indicated that pAPS exhibited greater anti-DHAV activity than APS and sAPS both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides

Wang

Chen

Yang

et al. 2016

Exp Biol Med (Maywood)

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“…Infection of other mammalian species by EMCV is often fatal and associated with outbreaks of myocarditis and encephalitis. Human EMCV infection and associated disease have been documented, but clinical manifestation is probably infrequent (1). Theilovirus species are classified into five types, two of which infect humans: Vilyuisk human encephalomyelitis virus and Saffold virus (9,10).…”

mentioning

confidence: 99%

“…he Picornaviridae family is one of the largest virus families known and includes many important human and animal pathogens, such as polioviruses (PV), human rhinoviruses (HRV), and foot-and-mouth disease virus (FMDV) (1,2). The Cardiovirus genus consists of two species: encephalomyocarditis virus (EMCV) and related viruses (mengovirus, Columbia SK virus, and Maus-Elberfeld virus) (3) and Theilovirus (4)(5)(6).…”

mentioning

confidence: 99%

The Crystal Structure of a Cardiovirus RNA-Dependent RNA Polymerase Reveals an Unusual Conformation of the Polymerase Active Site

Vives-Adrián

Lujan

Oliva

et al. 2014

J Virol

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Encephalomyocarditis virus (EMCV) is a member of the IMPORTANCEThe Picornaviridae family is one of the largest virus families known, including many important human and animal pathogens. The RNA-dependent RNA polymerase (RdRp) 3D pol is a key enzyme for picornavirus genome replication and a validated target for the development of antiviral therapies. Solving the X-ray structure of the first cardiovirus RdRp, EMCV 3D pol , we captured an altered conformation of a conserved motif in the polymerase active site (motif A) containing the aspartic acid residue involved in rNTP selection and binding. This altered conformation of motif A, which interferes with the correct positioning of the rNTP substrate in the active site, is stabilized by a number of residues strictly conserved among picornaviruses. The rearrangements observed suggest that this motif A segment is a dynamic element that can be modulated by external effectors, either activating or inhibiting enzyme activity, and this type of modulation appears to be general to all picornaviruses.

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“…However, until now there is only experimental data confirming the NTPase but not the helicase activity of this nonstructural protein of norovirus (Hardy, 2005). , 2008a;De Palma et al, 2008c;Norder et al, 2011) could as well be inhibitors of the NTPase of norovirus. The multiple mechanisms through which compounds could inhibit the helicase/NTPase have been extensively described elsewhere .…”

Section: Ntpasementioning

confidence: 99%

Targeting Norovirus: Strategies for the Discovery of New Antiviral Drugs

Rocha‐Pereira¹,

Nascimento²

2012

Antiviral Drugs - Aspects of Clinical Use and Recent Advances

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Picornavirus non-structural proteins as targets for new anti-virals with broad activity

Cited by 76 publications

References 149 publications

Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides

Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides

The Crystal Structure of a Cardiovirus RNA-Dependent RNA Polymerase Reveals an Unusual Conformation of the Polymerase Active Site

Targeting Norovirus: Strategies for the Discovery of New Antiviral Drugs

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