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Recent Advances in Targeting Dengue and West Nile Virus Proteases Using Small Molecule Inhibitors

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Therapy of Viral Infections

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

Abstract

Targeting viral proteases represents an attractive concept in the field of anti-infective lead discovery and has been exploited successfully yielding a number of drugs on the market. Next to their essential role in degrading the virus-encoded polyprotein to functionally relevant units, viral proteases can be involved in further processes relevant to viral replication such as interaction to host proteins. Despite the promising nature of this drug discovery concept in general, lead discovery strategies against flavivirus-caused diseases such as Dengue- and West Nile virus infections are still at a comparably early stage. In the present contribution, recent advances targeting the proteases of Dengue and West Nile viruses are reviewed.

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Abbreviations

Abz:

o-Aminobenzoic acid

Ac:

Acetyl

ACMC:

7-Amino-3-carbamoylmethyl-4-methyl-coumarin

Ag:

Agmatine, 4-aminobutylguanidine

AMC:

4-Methylcoumaryl-7-amide

BHK21:

Baby hamster kidney cells

Boc:

t-Butoxycarbonyl

Bz:

Benzoyl

Cit:

Citrulline

cmpd(s):

Compound(s)

CNS:

Central nervous system

DEV:

Dengue virus

DEVpro :

Dengue virus protease

DNS:

Dansyl

EDDnp:

N-(2,4-dinitrophenyl)ethylenediamine

FL:

Full length

GCMA:

trans-(4-guanidino)cyclohexylmethylamide

HTS:

High-throughput-screening

ITC:

Isothermal titration calorimetry

Itz:

Iminothiazolidine

2-Naph:

2-Naphthoyl

nL:

Norleucine

nY-NH2 :

3-Nitrotyrosineamide

O:

Hydroxyprolin

Orn:

Ornithine

PDB:

Protein data bank

pG:

Pyroglutamyl

Ph:

Phenyl

Phac:

Phenacetyl

PI:

Protease inhibitor

pNA:

para nitroanilide

SAR:

Structure–activity relationship

SAXS:

Small-angle X-ray scattering

SPR:

Surface plasmon resonance

WNV:

West Nile virus

WNVpro :

WNV protease

Z:

Benzyloxycarbonyl

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Authors and Affiliations

  1. Bayer Pharma AG, Lead Discovery Berlin – Structural Biology, Müllerstraße 178, 13353, Berlin, Germany

    Holger Steuber

  2. Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35037, Marburg, Germany

    Manuel Kanitz, Fabian G. R. Ehlert & Wibke E. Diederich

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  1. Holger Steuber
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  2. Manuel Kanitz
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  3. Fabian G. R. Ehlert
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  4. Wibke E. Diederich
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Correspondence to Holger Steuber or Wibke E. Diederich .

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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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Steuber, H., Kanitz, M., Ehlert, F.G.R., Diederich, W.E. (2014). Recent Advances in Targeting Dengue and West Nile Virus Proteases Using Small Molecule Inhibitors. 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_46

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