Structural investigation of cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly.

doi:10.1021/jm401560v

Paper

Structural investigation of cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly.

Published Dec 13, 2013 · Serena Massari, Giulio Nannetti, Laura Goracci

Journal of medicinal chemistry

Q1 SJR score

50

Citations

1

Influential Citations

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Abstract

The limited number of drug classes licensed for treatment of influenza virus (Flu), together with the continuous emergence of viral variants and drug resistant mutants, highlights the urgent need to find antivirals with novel mechanisms of action. In this context, the viral RNA-dependent RNA polymerase (RdRP) subunits assembly has emerged as an attractive target. Starting from a cycloheptathiophene-3-carboxamide derivative recently identified by us for its ability to disrupt the interaction between the PA and PB1 subunits of RdRP, we have designed and synthesized a series of analogues. Their biological evaluation led to the identification of more potent protein-protein interaction inhibitors, endowed with antiviral activity that also encompassed a number of clinical isolates of FluA, including an oseltamivir-resistant strain, and FluB, without showing appreciable toxicity. From this study, the cycloheptathiophene-3-carboxamide scaffold emerged as being particularly suitable to impart anti-Flu activity.

Study Snapshot

Cycloheptathiophene-3-carboxamide derivatives show potential as novel antivirals by disrupting influenza virus polymerase assembly, showing antiviral activity against FluA, FluB, and drug-resistant strains without significant toxicity.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Structural investigation of cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly.

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Citations

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