PandemieGrippaleV1, PascalFrancis, Checkpoint, bibRecord, 000186

The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus

Identifieur interne : 000186 ( PascalFrancis/Checkpoint ); précédent : 000185; suivant : 000187

The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus

Auteurs : Emanuel Haasbach [Allemagne] ; Sarah Julia Reiling [Allemagne] ; Christina Ehrhardt [Allemagne] ; Karoline Droebner [Allemagne] ; Andrea Rückle [Allemagne] ; Eike R. Hrincius [Allemagne] ; Johann Leban [Allemagne] ; Stefan Strobl [Allemagne] ; Daniel Vitt [Allemagne] ; Stephan Ludwig [Allemagne] ; Oliver Planz [Allemagne]

Source :

Antiviral research [ 0166-3542 ] ; 2013.

RBID : Pascal:13-0363806

Descripteurs français

Pascal (Inist)
- Inhibiteur, Prévention, Animal, Souris, Pathogène, Influenzavirus aviaire, Virus grippal A, Antiviral.

English descriptors

KwdEn :
- Animal, Antiviral, Avian influenzavirus, Influenza A virus, Inhibitor, Mouse, Pathogenic, Prevention.

Abstract

The appearance of pandemic H1N1 and highly pathogenic avian H5N1 viruses in humans as well as the emergence of seasonal H1N1 variants resistant against neuraminidase inhibitors highlight the urgent need for new and amply available antiviral drugs. We and others have demonstrated that influenza virus misuses the cellular IKK/NF-kappaB signaling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here, we show that the novel NF-kappaB inhibitor SC75741 significantly protects mice against infection with highly pathogenic avian influenza A viruses of the H5N1 and H7N7 subtypes. Treatment was efficient when SC75741 was given intravenously in a concentration of 5 mg/kg/day. In addition, application of SC75741 via the intraperitoneal route resulted in a high bioavailability and was also efficient against influenza when given 15 mg/kg/day or 7.5 mg/kg/twice a day. Protection was achieved when SC75741 was given for seven consecutive days either prior to infection or as late as four days after infection. SC75741 treatment showed no adverse effects in the concentrations required to protect mice against influenza virus infection. Although more pre-clinical studies are needed SC75741 might be a promising candidate for a novel antiviral drug against influenza viruses that targets the host cell rather than the virus itself.

Affiliations:

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Le document en format XML

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<front><div type="abstract" xml:lang="en">The appearance of pandemic H1N1 and highly pathogenic avian H5N1 viruses in humans as well as the emergence of seasonal H1N1 variants resistant against neuraminidase inhibitors highlight the urgent need for new and amply available antiviral drugs. We and others have demonstrated that influenza virus misuses the cellular IKK/NF-kappaB signaling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here, we show that the novel NF-kappaB inhibitor SC75741 significantly protects mice against infection with highly pathogenic avian influenza A viruses of the H5N1 and H7N7 subtypes. Treatment was efficient when SC75741 was given intravenously in a concentration of 5 mg/kg/day. In addition, application of SC75741 via the intraperitoneal route resulted in a high bioavailability and was also efficient against influenza when given 15 mg/kg/day or 7.5 mg/kg/twice a day. Protection was achieved when SC75741 was given for seven consecutive days either prior to infection or as late as four days after infection. SC75741 treatment showed no adverse effects in the concentrations required to protect mice against influenza virus infection. Although more pre-clinical studies are needed SC75741 might be a promising candidate for a novel antiviral drug against influenza viruses that targets the host cell rather than the virus itself.</div>
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<s5>354000501076070180</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2013 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>3/4 p.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>13-0363806</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Antiviral research</s0>
</fA64>
<fA66 i1="01"><s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>The appearance of pandemic H1N1 and highly pathogenic avian H5N1 viruses in humans as well as the emergence of seasonal H1N1 variants resistant against neuraminidase inhibitors highlight the urgent need for new and amply available antiviral drugs. We and others have demonstrated that influenza virus misuses the cellular IKK/NF-kappaB signaling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here, we show that the novel NF-kappaB inhibitor SC75741 significantly protects mice against infection with highly pathogenic avian influenza A viruses of the H5N1 and H7N7 subtypes. Treatment was efficient when SC75741 was given intravenously in a concentration of 5 mg/kg/day. In addition, application of SC75741 via the intraperitoneal route resulted in a high bioavailability and was also efficient against influenza when given 15 mg/kg/day or 7.5 mg/kg/twice a day. Protection was achieved when SC75741 was given for seven consecutive days either prior to infection or as late as four days after infection. SC75741 treatment showed no adverse effects in the concentrations required to protect mice against influenza virus infection. Although more pre-clinical studies are needed SC75741 might be a promising candidate for a novel antiviral drug against influenza viruses that targets the host cell rather than the virus itself.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02S05</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Inhibiteur</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Inhibitor</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Inhibidor</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Prévention</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Prevention</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Prevención</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Animal</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Animal</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Animal</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Souris</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Mouse</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Ratón</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Pathogène</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Pathogenic</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Patógeno</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Influenzavirus aviaire</s0>
<s2>NW</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Avian influenzavirus</s0>
<s2>NW</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Avian influenzavirus</s0>
<s2>NW</s2>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Virus grippal A</s0>
<s2>NW</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Influenza A virus</s0>
<s2>NW</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Influenza A virus</s0>
<s2>NW</s2>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Antiviral</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Antiviral</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Antiviral</s0>
<s5>08</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Influenzavirus A</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Influenzavirus A</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Influenzavirus A</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Orthomyxoviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Orthomyxoviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Orthomyxoviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fN21><s1>343</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>Bade-Wurtemberg</li>
<li>Bavière</li>
<li>District de Haute-Bavière</li>
<li>District de Tübingen</li>
</region>
<settlement><li>Munich</li>
<li>Tübingen</li>
</settlement>
</list>
<tree><country name="Allemagne"><noRegion><name sortKey="Haasbach, Emanuel" sort="Haasbach, Emanuel" uniqKey="Haasbach E" first="Emanuel" last="Haasbach">Emanuel Haasbach</name>
</noRegion>
<name sortKey="Droebner, Karoline" sort="Droebner, Karoline" uniqKey="Droebner K" first="Karoline" last="Droebner">Karoline Droebner</name>
<name sortKey="Ehrhardt, Christina" sort="Ehrhardt, Christina" uniqKey="Ehrhardt C" first="Christina" last="Ehrhardt">Christina Ehrhardt</name>
<name sortKey="Hrincius, Eike R" sort="Hrincius, Eike R" uniqKey="Hrincius E" first="Eike R." last="Hrincius">Eike R. Hrincius</name>
<name sortKey="Leban, Johann" sort="Leban, Johann" uniqKey="Leban J" first="Johann" last="Leban">Johann Leban</name>
<name sortKey="Ludwig, Stephan" sort="Ludwig, Stephan" uniqKey="Ludwig S" first="Stephan" last="Ludwig">Stephan Ludwig</name>
<name sortKey="Planz, Oliver" sort="Planz, Oliver" uniqKey="Planz O" first="Oliver" last="Planz">Oliver Planz</name>
<name sortKey="Reiling, Sarah Julia" sort="Reiling, Sarah Julia" uniqKey="Reiling S" first="Sarah Julia" last="Reiling">Sarah Julia Reiling</name>
<name sortKey="Ruckle, Andrea" sort="Ruckle, Andrea" uniqKey="Ruckle A" first="Andrea" last="Rückle">Andrea Rückle</name>
<name sortKey="Strobl, Stefan" sort="Strobl, Stefan" uniqKey="Strobl S" first="Stefan" last="Strobl">Stefan Strobl</name>
<name sortKey="Vitt, Daniel" sort="Vitt, Daniel" uniqKey="Vitt D" first="Daniel" last="Vitt">Daniel Vitt</name>
</country>
</tree>
</affiliations>
</record>

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The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus

The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus

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