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

TitleBPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses.
Authors
KeywordsAntiviral agent
Influenza A virus
Viral RNA
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://jac.oxfordjournals.org/
Citation
The Journal Of Antimicrobial Chemotherapy, 2010, v. 65 n. 1, p. 63-71 How to Cite?
AbstractOBJECTIVES: 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 (EC(50) ranging from 0.021 to 0.040 microM). 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.
Persistent Identifierhttp://hdl.handle.net/10722/125129
ISSN
2015 SCImago Journal Rankings: 2.157
ISI Accession Number ID
Funding AgencyGrant Number
The National Science Council of the Republic of China, TaiwanNSC-97-2321-B-182-003
Research Grant Council of Hong KongHKU 7530/06M
Funding Information:

The National Science Council of the Republic of China, Taiwan, financially supported this research under contract no. NSC-97-2321-B-182-003. This project was also partly supported by the Research Grant Council of Hong Kong (HKU 7530/06M, L. L. M. P.).

Grants

 

DC FieldValueLanguage
dc.contributor.authorShih, SRen_HK
dc.contributor.authorHorng, JTen_HK
dc.contributor.authorPoon, LLen_HK
dc.contributor.authorChen, TCen_HK
dc.contributor.authorYeh, JYen_HK
dc.contributor.authorHsieh, HPen_HK
dc.contributor.authorTseng, SNen_HK
dc.contributor.authorChiang, Cen_HK
dc.contributor.authorLi, WLen_HK
dc.contributor.authorChao, YSen_HK
dc.contributor.authorHsu, JTen_HK
dc.date.accessioned2010-10-31T11:13:02Z-
dc.date.available2010-10-31T11:13:02Z-
dc.date.issued2010en_HK
dc.identifier.citationThe Journal Of Antimicrobial Chemotherapy, 2010, v. 65 n. 1, p. 63-71en_HK
dc.identifier.issn1460-2091en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125129-
dc.description.abstractOBJECTIVES: 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 (EC(50) ranging from 0.021 to 0.040 microM). 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.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://jac.oxfordjournals.org/-
dc.relation.ispartofThe Journal of antimicrobial chemotherapyen_HK
dc.subjectAntiviral agenten_HK
dc.subjectInfluenza A virusen_HK
dc.subjectViral RNAen_HK
dc.titleBPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses.en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0305-7453&volume=65&issue=1&spage=63&epage=71&date=2010&atitle=BPR2-D2+targeting+viral+ribonucleoprotein+complex-associated+function+inhibits+oseltamivir-resistant+influenza+virusesen_HK
dc.identifier.emailPoon, LL: llmpoon@hkucc.hku.hken_HK
dc.identifier.authorityPoon, LL=rp00484en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/jac/dkp393en_HK
dc.identifier.pmid19892833-
dc.identifier.scopuseid_2-s2.0-77950356637en_HK
dc.identifier.hkuros176300en_HK
dc.identifier.volume65en_HK
dc.identifier.issue1en_HK
dc.identifier.spage63en_HK
dc.identifier.epage71en_HK
dc.identifier.isiWOS:000272931500010-
dc.relation.projectStudies of mammalian, avian and chimeric influenza polymerase complexes-
dc.identifier.scopusauthoridShih, SR=7201649446en_HK
dc.identifier.scopusauthoridHorng, JT=7103277761en_HK
dc.identifier.scopusauthoridPoon, LL=7005441747en_HK
dc.identifier.scopusauthoridChen, TC=7405545332en_HK
dc.identifier.scopusauthoridYeh, JY=8085740000en_HK
dc.identifier.scopusauthoridHsieh, HP=7201610786en_HK
dc.identifier.scopusauthoridTseng, SN=24391578600en_HK
dc.identifier.scopusauthoridChiang, C=25631693100en_HK
dc.identifier.scopusauthoridLi, WL=35603969600en_HK
dc.identifier.scopusauthoridChao, YS=7402864078en_HK
dc.identifier.scopusauthoridHsu, JT=7402284125en_HK

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