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Article: Cross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain

TitleCross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain
Authors
Issue Date2015
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://aac.asm.org/
Citation
Antimicrobial Agents and Chemotherapy, 2015, v. 59 n. 7, p. 4082-4093 How to Cite?
AbstractAmino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PAN is highly conserved among different subtypes of influenza virus, which suggests PAN to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PAN domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PAN were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs.
Persistent Identifierhttp://hdl.handle.net/10722/214393
ISSN
2020 Impact Factor: 5.191
2020 SCImago Journal Rankings: 2.070
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYuan, S-
dc.contributor.authorZhang, N-
dc.contributor.authorSingh, K-
dc.contributor.authorShuai, H-
dc.contributor.authorChu, H-
dc.contributor.authorZhou, J-
dc.contributor.authorChow, BKC-
dc.contributor.authorZheng, B-
dc.date.accessioned2015-08-21T11:22:19Z-
dc.date.available2015-08-21T11:22:19Z-
dc.date.issued2015-
dc.identifier.citationAntimicrobial Agents and Chemotherapy, 2015, v. 59 n. 7, p. 4082-4093-
dc.identifier.issn0066-4804-
dc.identifier.urihttp://hdl.handle.net/10722/214393-
dc.description.abstractAmino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PAN is highly conserved among different subtypes of influenza virus, which suggests PAN to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PAN domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PAN were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs.-
dc.languageeng-
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://aac.asm.org/-
dc.relation.ispartofAntimicrobial Agents and Chemotherapy-
dc.titleCross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain-
dc.typeArticle-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailChow, BKC: bkcc@hku.hk-
dc.identifier.emailZheng, B: bzheng@hkucc.hku.hk-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityChow, BKC=rp00681-
dc.identifier.authorityZheng, B=rp00353-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/AAC.00306-15-
dc.identifier.pmid25918143-
dc.identifier.pmcidPMC4468670-
dc.identifier.scopuseid_2-s2.0-84935856083-
dc.identifier.hkuros246817-
dc.identifier.volume59-
dc.identifier.issue7-
dc.identifier.spage4082-
dc.identifier.epage4093-
dc.identifier.isiWOS:000360896000048-
dc.publisher.placeUnited States-
dc.identifier.issnl0066-4804-

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