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β-Lactams as flaviviral NS3 protease inhibitors

Total Cost €


EC-Contrib. €






 LIsTEN project word cloud

Explore the words cloud of the LIsTEN project. It provides you a very rough idea of what is the project "LIsTEN" about.

near    acids    enzyme    denv    synthesized    consist    inhibitory    group    moiety    exist    reduce    infections    global    flaviviral    west    diseases    previously    united    treatment    natural    warheads    active    dengue    adriatic    bond    valuable    people    protease    potency    selectivity    regions    membrane    host    affinity    purpose    agents    moment    billion    mediterranean    asia    lactams    medical    catalytic    significantly    stability    off    covalent    derivatives    serine    wnv    strategy    coast    cell    spread    nile    improvement    beta    emerged    ameliorate    virus    unnatural    inhibitors    outbreak    warhead    permeability    threat    disease    binding    sub    assays    ns3    metabolic    zikv    peptide    site    living    possibility    warming    inhibitor    act    tropical    residue    culture    climate    zika    potent    biochemical    amino    moderate    incorporation    electrophilic    compounds    consequence    replication    parts    accordingly    america    lactam    coupled   

Project "LIsTEN" data sheet

The following table provides information about the project.


Organization address
postcode: 69117

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website
 Total cost 171˙460 €
 EC max contribution 171˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-05-02   to  2019-05-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Flaviviral infections already represent a threat to 2.5 billion people living in tropical and sub-tropical regions. As a consequence of climate change and global warming in the near future these infections are expected to spread to areas with moderate climate and the possibility of disease outbreak will exist in Europe, especially around the Mediterranean and Adriatic coast, as well as in the United States of America and large parts of Asia. At the moment no medical treatment against flaviviral diseases is available. Recently, peptide-based compounds which act as flaviviral NS3 protease inhibitors, emerged as potent agents against dengue virus (DENV), Zika virus (ZIKV) and West Nile virus (WNV). These compounds consist of two to four natural or unnatural amino acids and act by binding to the active site of the protease. Accordingly, the incorporation of an electrophilic warhead, a moiety which would facilitate the covalent binding of the inhibitor to the catalytic serine residue, into the peptide inhibitor represents a valuable strategy for the improvement of potency of such inhibitors. The goal of the proposed project is to investigate the potential of β-lactams as electrophilic warheads in DENV, ZIKV and WNV protease inhibitors. For that purpose, new β-lactam derivatives will be synthesized, coupled to peptide inhibitors previously developed by the host group and their affinity to the target will be evaluated by biochemical assays. The most potent compounds will be characterized in more detail and their activity against dengue virus replication in cell culture, off-target binding, membrane permeability and metabolic stability will be studied. We expect the formation of a covalent bond between inhibitor and active site of the enzyme to significantly improve inhibitory activity by increasing binding affinity, as well as to ameliorate selectivity and reduce off-target binding.


year authors and title journal last update
List of publications.
2019 Tonko Dražić, Sara Kopf, James Corridan, Mila M. Leuthold, Branimir Bertoša, Christian D. Klein
Peptide-β-lactam Inhibitors of Dengue and West Nile Virus NS2B-NS3 Protease Display Two Distinct Binding Modes
published pages: 140-156, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.9b00759
Journal of Medicinal Chemistry 63/1 2020-02-12

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The information about "LISTEN" are provided by the European Opendata Portal: CORDIS opendata.

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