H2N2V1, Main, Exploration, bibRecord, 000F25

BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses

Identifieur interne : 000F25 ( Main/Exploration ); précédent : 000F24; suivant : 000F26

BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses

Auteurs : Shin-Ru Shih [Taïwan] ; Jim-Tong Horng [Taïwan] ; Leo L. M. Poon [République populaire de Chine] ; Tzu-Chun Chen [Taïwan] ; Jiann-Yih Yeh [Taïwan] ; Hsing-Pang Hsieh [Taïwan] ; Sung-Nain Tseng [Taïwan] ; Chiayn Chiang [Taïwan] ; Wan-Ling Li [Taïwan] ; Yu-Sheng Chao [Taïwan] ; John T.-A. Hsu [Taïwan]

Source :

Journal of Antimicrobial Chemotherapy [ 0305-7453 ] ; 2010.

RBID : ISTEX:664E0190D6FF9382BBA3AAFB0E776FDABDA9011B

Abstract

Objectives The emergence of oseltamivir-resistant viruses raised the global threat with regard to influenza virus infection. To develop alternative antiviral agents against influenza virus infection is significant and urgent. Methods A neutralization test was applied as a screening assay and a plaque reduction assay was used for confirmation. Expression plasmids for viral ribonucleoproteins (RNPs) and a plasmid that allowed expression of a pseudoviral reporter RNA were transfected into cells to investigate the effects of a novel antiviral compound on viral RNA synthesis. Results BPR2-D2 was identified as a novel inhibitor against influenza virus from a hit obtained from high throughput screening of 20 000 or more compounds. BPR2-D2 exhibited an excellent antiviral efficacy for the oseltamivir-resistant virus (EC50 ranging from 0.021 to 0.040 µM). No resistant virus was produced throughout 20 passages in the presence of BPR2-D2, whereas oseltamivir-resistant virus was generated at passage 8 using the same experimental system. A molecular target other than neuraminidase (NA) was found because BPR2-D2 inhibited the synthesis of viral RNA that was driven by influenza viral RNP in a transfection assay. BPR2-D2 also exhibited a broad antiviral spectrum against various strains of influenza A and influenza B viruses. Conclusions BPR2-D2 was identified as a novel inhibitor of influenza virus. It may target viral RNPs that are responsible for viral RNA synthesis. Targeting different molecules compared with NA allows BPR2-D2 to inhibit oseltamivir-resistant viruses.

Url:

https://api.istex.fr/ark:/67375/HXZ-9V25P41P-R/fulltext.pdf

DOI: 10.1093/jac/dkp393

Affiliations:

République populaire de Chine, Taïwan

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to stream Main, to step Curation: 000F25

Le document en format XML

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<front><div type="abstract">Objectives The emergence of oseltamivir-resistant viruses raised the global threat with regard to influenza virus infection. To develop alternative antiviral agents against influenza virus infection is significant and urgent. Methods A neutralization test was applied as a screening assay and a plaque reduction assay was used for confirmation. Expression plasmids for viral ribonucleoproteins (RNPs) and a plasmid that allowed expression of a pseudoviral reporter RNA were transfected into cells to investigate the effects of a novel antiviral compound on viral RNA synthesis. Results BPR2-D2 was identified as a novel inhibitor against influenza virus from a hit obtained from high throughput screening of 20 000 or more compounds. BPR2-D2 exhibited an excellent antiviral efficacy for the oseltamivir-resistant virus (EC50 ranging from 0.021 to 0.040 µM). No resistant virus was produced throughout 20 passages in the presence of BPR2-D2, whereas oseltamivir-resistant virus was generated at passage 8 using the same experimental system. A molecular target other than neuraminidase (NA) was found because BPR2-D2 inhibited the synthesis of viral RNA that was driven by influenza viral RNP in a transfection assay. BPR2-D2 also exhibited a broad antiviral spectrum against various strains of influenza A and influenza B viruses. Conclusions BPR2-D2 was identified as a novel inhibitor of influenza virus. It may target viral RNPs that are responsible for viral RNA synthesis. Targeting different molecules compared with NA allows BPR2-D2 to inhibit oseltamivir-resistant viruses.</div>
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BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses

BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses

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Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

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