Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.

<h4>Background</h4>Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs ar...

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Autores principales:	Anwar M Hashem, Anathea S Flaman, Aaron Farnsworth, Earl G Brown, Gary Van Domselaar, Runtao He, Xuguang Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c50601ec06944ec1a972842046281b41
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spelling	oai:doaj.org-article:c50601ec06944ec1a972842046281b412021-11-25T06:27:18ZAurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.1932-620310.1371/journal.pone.0008350https://doaj.org/article/c50601ec06944ec1a972842046281b412009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20020057/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies.<h4>Methodology/principal findings</h4>We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus.<h4>Conclusions/significance</h4>Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride.Anwar M HashemAnathea S FlamanAaron FarnsworthEarl G BrownGary Van DomselaarRuntao HeXuguang LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8350 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anwar M Hashem Anathea S Flaman Aaron Farnsworth Earl G Brown Gary Van Domselaar Runtao He Xuguang Li Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
description	<h4>Background</h4>Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies.<h4>Methodology/principal findings</h4>We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus.<h4>Conclusions/significance</h4>Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride.
format	article
author	Anwar M Hashem Anathea S Flaman Aaron Farnsworth Earl G Brown Gary Van Domselaar Runtao He Xuguang Li
author_facet	Anwar M Hashem Anathea S Flaman Aaron Farnsworth Earl G Brown Gary Van Domselaar Runtao He Xuguang Li
author_sort	Anwar M Hashem
title	Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
title_short	Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
title_full	Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
title_fullStr	Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
title_full_unstemmed	Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
title_sort	aurintricarboxylic acid is a potent inhibitor of influenza a and b virus neuraminidases.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/c50601ec06944ec1a972842046281b41
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Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.

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