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Strategies for the Development of Influenza Drugs: Basis for New Efficient Combination Therapies

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Book cover Therapy of Viral Infections

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 15))

Abstract

Only four drugs are approved for the specific treatment of acute influenza infections worldwide. These drugs address either the viral neuraminidase or the M2-channel but suffer from poor efficacy and the rapid emergence of drug resistances. Some additional drugs are launched in few countries, but their efficacy is relatively low and often limited to certain influenza strains. Ideally, new drugs should possess a broad potency against all influenza viruses and be less susceptible to the development of resistances. The propagation cycle of the influenza virus offers many possibilities for the development of new anti-influenza drugs. Various compounds addressing viral targets reached clinical development, from which the most-advanced candidate is the polymerase inhibitor favipiravir. A promising strategy could be also the inhibition of host targets and signaling pathways, e.g., by already approved kinase inhibitors, anti-inflammatory drugs, or immunomodulatory agents. However, the benefit of these agents has to be demonstrated in controlled clinical trials. A broader arsenal of approved drugs will offer the possibility for more efficient combinatorial therapies in the future. The first proof of concept studies for such multiple drug therapies in infected mice revealed beneficial effects. Moreover, this strategy should reduce the rapid emergence of resistant influenza strains.

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Abbreviations

dsRNA:

Double-stranded RNA

HA:

Hemagglutinin

HCV:

Hepatitis C virus

HPAIV:

Highly pathogenic avian influenza virus

HTS:

High-throughput screening

IFN:

Interferon

NA:

Neuraminidase

nAb:

Neutralizing antibody

NAI:

Neuraminidase inhibitor

NEP:

Nuclear export protein

NP:

Nucleoprotein

RdRp:

RNA-dependent RNA polymerase

RNP:

Ribonucleoprotein

SA:

Sialic acid

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Authors and Affiliations

  1. Institute of Pharmaceutical Chemistry, Philipps University, Marbacher Weg 6, 35032, Marburg, Germany

    Torsten Steinmetzer & Kornelia Hardes

  2. Institute of Virology, Philipps University, Hans-Meerwein-Str. 2, 35043, Marburg, Germany

    Eva Böttcher-Friebertshäuser & Wolfgang Garten

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  1. Torsten Steinmetzer
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  2. Kornelia Hardes
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  3. Eva Böttcher-Friebertshäuser
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  4. Wolfgang Garten
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Correspondence to Torsten Steinmetzer .

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  1. Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marburg, Germany

    Wibke E. Diederich

  2. -, Bayer Pharma AG, Lead Discovery Berlin - Structural Biology, Berlin, Germany

    Holger Steuber

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Steinmetzer, T., Hardes, K., Böttcher-Friebertshäuser, E., Garten, W. (2014). Strategies for the Development of Influenza Drugs: Basis for New Efficient Combination Therapies. In: Diederich, W., Steuber, H. (eds) Therapy of Viral Infections. Topics in Medicinal Chemistry, vol 15. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2014_84

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