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Antiviral Res. 2013 Aug 1. pii: S0166-3542(13)00201-5. doi: 10.1016/j.antiviral.2013.07.014. [Epub ahead of print]
Anti-influenza A virus activity of uridine derivatives of 2-deoxy sugars.
Krol E, Wandzik I, Gromadzka B, Nidzworski D, Rychlowska M, Matlacz M, Tyborowska J, Szewczyk B.
Source
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland. Electronic address: ewelina@biotech.ug.gda.pl.
Abstract
Influenza viruses are important pathogens that cause respiratory infections in humans and animals. Apart from vaccinations, antiviral drugs play a significant role in controlling spread of the disease. Influenza A virus contains two membrane glycoproteins on the external part of viral envelope: hemagglutinin (HA) and neuraminidase (NA), which are crucial for productive infection in target cells. In the present work,two derivatives of tunicamycin - uridine derivatives of 2-deoxy sugars (designated IW3 and IW7),which target the glycan processing steps duringmaturation of viral glycoproteins,were assayed for their ability to inhibit influenza A virus infectionin vitro.Using the cytopathic effect (CPE) inhibition assay and viral plaque reduction assay we showed, that both IW3 and IW7 inhibitors exerted significant inhibitory effect on influenza A virus infection in MDCK cells without significant toxicity for the cells. Moreover, tested compounds selectively suppressed viral protein expression in a dose-dependent manner, suggesting that the mechanism of their antiviral activity may be similarto this shown previously for other viruses. We have also excluded the possibility that both inhibitors act at the replication step of virus life cycle. Using real-time PCR assay it was shown that IW3 and IW7 did not change the level of viral RNAin infected MDCK cells after a single round of infection. Therefore, inhibition of influenza A virus infection by uridine derivatives of 2-deoxy sugars,acting as glycosylation inhibitors, is apromisingalternative approach for the development of new anti-influenza A therapy.
Copyright ? 2013. Published by Elsevier B.V.
KEYWORDS:
CC(50), CPE, CSFV, Ct, ER, Glycoproteins, Glycosylation inhibition, HA, IC(50), Influenza A virus, L-1-Tosylamide-2-phenylethyl chloromethyl ketone, MDCK, MOI, Madin-Darby canine kidney cells, NA, S.D., S.I., Sf9, Spodopterafrugiperdainsect cell line, TPCK, Tunicamycin derivatives, classical swine fever virus, concentration of the compound required to reduce cell viability by 50%, concentration of the compound required to reduce virus plaque formation by 50%, cycle threshold, cytopathic effect, endoplasmic reticulum, hemagglutinin, multiplicity of infection, neuraminidase, selectivity index, standard deviations
PMID:
23911991
[PubMed - as supplied by publisher]
Anti-influenza A virus activity of uridine derivatives of 2-deoxy sugars.
Krol E, Wandzik I, Gromadzka B, Nidzworski D, Rychlowska M, Matlacz M, Tyborowska J, Szewczyk B.
Source
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland. Electronic address: ewelina@biotech.ug.gda.pl.
Abstract
Influenza viruses are important pathogens that cause respiratory infections in humans and animals. Apart from vaccinations, antiviral drugs play a significant role in controlling spread of the disease. Influenza A virus contains two membrane glycoproteins on the external part of viral envelope: hemagglutinin (HA) and neuraminidase (NA), which are crucial for productive infection in target cells. In the present work,two derivatives of tunicamycin - uridine derivatives of 2-deoxy sugars (designated IW3 and IW7),which target the glycan processing steps duringmaturation of viral glycoproteins,were assayed for their ability to inhibit influenza A virus infectionin vitro.Using the cytopathic effect (CPE) inhibition assay and viral plaque reduction assay we showed, that both IW3 and IW7 inhibitors exerted significant inhibitory effect on influenza A virus infection in MDCK cells without significant toxicity for the cells. Moreover, tested compounds selectively suppressed viral protein expression in a dose-dependent manner, suggesting that the mechanism of their antiviral activity may be similarto this shown previously for other viruses. We have also excluded the possibility that both inhibitors act at the replication step of virus life cycle. Using real-time PCR assay it was shown that IW3 and IW7 did not change the level of viral RNAin infected MDCK cells after a single round of infection. Therefore, inhibition of influenza A virus infection by uridine derivatives of 2-deoxy sugars,acting as glycosylation inhibitors, is apromisingalternative approach for the development of new anti-influenza A therapy.
Copyright ? 2013. Published by Elsevier B.V.
KEYWORDS:
CC(50), CPE, CSFV, Ct, ER, Glycoproteins, Glycosylation inhibition, HA, IC(50), Influenza A virus, L-1-Tosylamide-2-phenylethyl chloromethyl ketone, MDCK, MOI, Madin-Darby canine kidney cells, NA, S.D., S.I., Sf9, Spodopterafrugiperdainsect cell line, TPCK, Tunicamycin derivatives, classical swine fever virus, concentration of the compound required to reduce cell viability by 50%, concentration of the compound required to reduce virus plaque formation by 50%, cycle threshold, cytopathic effect, endoplasmic reticulum, hemagglutinin, multiplicity of infection, neuraminidase, selectivity index, standard deviations
PMID:
23911991
[PubMed - as supplied by publisher]
