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SILVER

Small-molecule Inhibitor Leads Versus emerging and neglected RNA viruses

Coordinatore	UNIVERSITE D'AIX MARSEILLE Organization address address: Boulevard Charles Livon 58 city: Marseille postcode: 13284 contact info Titolo: Ms. Nome: Céline Cognome: Damon Email: send email Telefono: 33491998595
Nazionalità Coordinatore	France [FR]
Totale costo	21˙899˙739 €
EC contributo	12˙000˙000 €
Programma	FP7-HEALTH Specific Programme "Cooperation": Health
Code Call	FP7-HEALTH-2010-single-stage
Funding Scheme	CP-IP
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-10-01 - 2015-03-31

Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITE D'AIX MARSEILLE Organization address address: Boulevard Charles Livon 58 city: Marseille postcode: 13284 contact info Titolo: Ms. Nome: Céline Cognome: Damon Email: send email Telefono: 33491998595	FR (Marseille)	coordinator	2˙855˙357.20
2	KATHOLIEKE UNIVERSITEIT LEUVEN Organization address address: Oude Markt 13 city: LEUVEN postcode: 3000 contact info Titolo: Dr. Nome: Elke Cognome: Lammertyn Email: send email Telefono: +32 16 32 06 21 Fax: +32 16 326515	BE (LEUVEN)	participant	993˙880.00
3	UNIVERSITAET ZU LUEBECK Organization address address: RATZEBURGER ALLEE 160 city: LUEBECK postcode: 23538 contact info Titolo: Dr. Nome: Margret Cognome: Schwab Email: send email Telefono: +49 451 5004062 Fax: +49 451 5004068	DE (LUEBECK)	participant	945˙400.00
4	ACADEMISCH ZIEKENHUIS LEIDEN Organization address address: Albinusdreef 2 city: LEIDEN postcode: 2333 ZA contact info Titolo: Ms. Nome: Marlien Cognome: Vos Email: send email Telefono: +31 71 526 1302 Fax: +31 71 526 6761	NL (LEIDEN)	participant	744˙609.60
5	AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS Organization address address: CALLE SERRANO 117 city: MADRID postcode: 28006 contact info Titolo: Mr. Nome: Eusebio Cognome: Jiménez Arroyo Email: send email Telefono: +34 91 566 8852 Fax: +34 91 566 89 13	ES (MADRID)	participant	624˙999.56
6	ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Organization address address: 's Gravendijkwal 230 city: ROTTERDAM postcode: 3015CE contact info Titolo: Mr. Nome: Wim Cognome: Leep Email: send email Telefono: +31 10 704 3451 Fax: +31 10 704 4760	NL (ROTTERDAM)	participant	589˙400.00
7	UNIVERSITA DEGLI STUDI DI MILANO Organization address address: Via Festa Del Perdono 7 city: MILANO postcode: 20122 contact info Titolo: Dr. Nome: Stefania Cognome: Varotto Email: send email Telefono: +39 2 50315037 Fax: +39 2 50315040	IT (MILANO)	participant	543˙000.00
8	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Organization address address: University Offices, Wellington Square city: OXFORD postcode: OX1 2JD contact info Titolo: Ms. Nome: Linda Cognome: Polik Email: send email Telefono: +44 1865 289800 Fax: +44 1865 289801	UK (OXFORD)	participant	500˙000.00
9	INSTITUT PASTEUR Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 contact info Titolo: Dr. Nome: Nadia Cognome: Khelef Email: send email Telefono: +33 1 40 61 33 78 Fax: +33 1 40 61 39 40	FR (PARIS CEDEX 15)	participant	418˙959.60
10	CENTRUM VOOR INNOVATIE EN STIMULATIEVAN MEDICIJNONTWIKKELING LEUVEN VZW Organization address address: MINDERBROEDERSTRAAT 12 city: LEUVEN postcode: 3000 contact info Titolo: Dr. Nome: Patrick Cognome: Chaltin Email: send email Telefono: +32 16 32 65 23 Fax: +32 16 33 29 68	BE (LEUVEN)	participant	403˙000.00
11	Global Phasing Limited Organization address address: Newton Road 43 city: CAMBRIDGE postcode: CB2 8AL contact info Titolo: Dr. Nome: Gerard Cognome: Bricogne Email: send email Telefono: +1223 353033 Fax: +1223 366889	UK (CAMBRIDGE)	participant	400˙000.00
12	UNIVERSITAETSKLINIKUM HEIDELBERG Organization address address: IM NEUENHEIMER FELD 672 city: HEIDELBERG postcode: 69120 contact info Titolo: Mr. Nome: Thorsten Cognome: Brietz Email: send email Telefono: +49 6221 56 7086 Fax: +49 6221 56 5460	DE (HEIDELBERG)	participant	400˙000.00
13	UNIVERSITAET HAMBURG Organization address address: EDMUND-SIEMERS-ALLEE 1 city: HAMBURG postcode: 20146 contact info Titolo: Mr. Nome: Jens Cognome: Bricke Email: send email Telefono: +49 40 428 38 2880 Fax: +49 40 428 38 2892	DE (HAMBURG)	participant	375˙000.00
14	UNIVERSITAET INNSBRUCK Organization address address: INNRAIN 52 city: INNSBRUCK postcode: 6020 contact info Titolo: Dr. Nome: Kurt Cognome: Habitzel Email: send email Telefono: +43 512 507 9051 Fax: +43 512 507 2607	AT (INNSBRUCK)	participant	375˙000.00
15	RIBOXX GMBH Organization address address: MEISSNER STRASSE 191 city: RADEBEUL postcode: 1445 contact info Titolo: Dr. Nome: Jacques Cognome: Rohayem Email: send email Telefono: +49 351 4586200 Fax: +49 351 4586314	DE (RADEBEUL)	participant	361˙720.00
16	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Mr. Nome: Jocelyn Cognome: Mere Email: send email Telefono: +33 4 67 61 35 35 Fax: +33 4 67 04 32 36	FR (PARIS)	participant	350˙000.00
17	UNIVERSITAET LEIPZIG Organization address address: RITTERSTRASSE 26 city: LEIPZIG postcode: 4109 contact info Titolo: Mr. Nome: Gerhard Cognome: Fuchs Email: send email Telefono: +49 341 9735012 Fax: +49 341 9735009	DE (LEIPZIG)	participant	282˙674.60
18	UNIVERSITEIT UTRECHT Organization address address: Heidelberglaan 8 city: UTRECHT postcode: 3584 CS contact info Titolo: Mrs. Nome: Louise Cognome: Van Der Kaaden Email: send email Telefono: +31 30 2535388 Fax: +31 30 2532333	NL (UTRECHT)	participant	230˙017.28
19	"SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES" Organization address address: ZU CHONG ZHI ROAD ZHANG JIANG High-Tech Park 555 city: SHANGHAI postcode: 201203 contact info Titolo: Ms. Nome: Jianmei Cognome: Shi Email: send email Telefono: +86 21 50807042 Fax: +86 21 50807042	CN (SHANGHAI)	participant	175˙000.00
20	STICHTING KATHOLIEKE UNIVERSITEIT Organization address address: GEERT GROOTEPLEIN NOORD 9 city: NIJMEGEN postcode: 6525 EZ contact info Titolo: Mr. Nome: Wim Cognome: Van Oijen Email: send email Telefono: +31 243618937 Fax: +31 243540529	NL (NIJMEGEN)	participant	144˙982.72
21	PIKE PHARMA GMBH Organization address address: TECHNOPARKSTRASSE 1 city: ZUERICH postcode: CH-8005 contact info Titolo: Dr. Nome: Ulrich Cognome: Kessler Email: send email Telefono: +41 44 633 73 53 Fax: +41 44 633 13 67	CH (ZUERICH)	participant	144˙673.94
22	FREIE UNIVERSITAET BERLIN Organization address address: Kaiserswertherstrasse 16-18 city: BERLIN postcode: 14195 contact info Titolo: Mr. Nome: Carsten Cognome: Malmwieck Email: send email Telefono: +49 30 83852990 Fax: +49 30 83853448	DE (BERLIN)	participant	142˙325.42
23	KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY Organization address address: JANG DONG YUSUNG GU 100 city: DAEJEON postcode: 305606 contact info Titolo: Dr. Nome: Youngjoo Cognome: Ko Email: send email Telefono: +82 42 860 7760 Fax: +82 42 860 7761	KR (DAEJEON)	participant	0.00
24	National Central University Organization address address: JHONGDA ROAD 300 city: Jhongli postcode: 320 contact info Titolo: Ms. Nome: Yu-Jin Cognome: Cheng Email: send email Telefono: +886 35 715131 Fax: +886 35 737322	TW (Jhongli)	participant	0.00

Mappa

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compound proteins molecule drug enzymes inhibitors inhibitor leads models neglected hits promising optimisation pipeline proof compounds relatively dengue screening cov silver protein drugs virus sars molecules economic versus antiviral viruses human small group medicinal structural discovery rna vitro mers viral

Obiettivo del progetto (Objective)

'RNA virus infections kill millions of humans annually, largely due to the lack of suitable vaccines and drugs to control them. This problem is addressed in this FP7 call and in response a consortium of Europe’s and Asia’s leading molecular virologists, structural biologists, medicinal chemists and bioinformaticians has been brought together to generate a state-of-the-art drug discovery and design programme. The project aims to identify Small molecule Inhibitor Leads Versus Emerging and neglected RNA viruses (SILVER). It will focus its activities on selected medically important RNA viruses for which the development of drugs is considered essential (Dengue-, entero- and paramyxoviruses), whereas other relatively neglected and/or emerging RNA viruses will be explored to identify the most promising viral protein targets and antiviral compounds. A pipeline strategy has been developed to enable the inclusion in SILVER of viruses at all levels of existing knowledge. Targets for potential drugs include infectious virus, structurally characterised viral enzymes and other proteins. Leads for currently available antiviral drugs have been identified by screening compound libraries in virus-infected cell culture systems and in vitro assays using purified viral enzymes. Selective inhibitors of viral replication have also been (and are being) derived using detailed structural knowledge of viral proteins and structure-based drug design. Hits will be assayed using individual viral protein targets and replicative proteins in complex with viral RNA. The potential protective activity of the most potent inhibitors, that have a favourable (in vitro) ADME-tox profile, will be assessed in relevant infection models in animals. Licenses on promising compounds or compound classes will be presented to the interested pharmaceutical industry. The SILVER consortium will be well placed to play a major role in contributing to the international effort to develop strategies to improve world health.'

Introduzione (Teaser)

EU funding is continuing to work on therapies to tackle emerging and neglected RNA viruses. Diseases include the newly emerging human MERS and severe acute respiratory syndrome (SARS).

Descrizione progetto (Article)

The 'Small-molecule inhibitor leads versus emerging and neglected RNA viruses' (http://www.silver-europe.com/ (SILVER)) project has completed another year of research on the priority group A viruses and relatively neglected and or emerging group B viruses.

The first two years of the SILVER project resulted in many hits and leads against a huge range of RNA viruses. Research response is keeping up with the all-too-rapid evolution and opportunistic behaviour of viruses.

The unexpected emergence of the human MERS-coronavirus (MERS CoV) in Saudi Arabia initiated an immediate response from the SILVER steering committee. Consequently, the project's 'Outbreak Pipeline' was activated to organise investigation into this potentially highly pathogenic virus.

The focus on optimisation of hit-to-lead has intensified delivering several priority lead compounds for a wide range of RNA viruses.

The researchers have identified and tested a very broad-spectrum inhibitor T705. There is also progress on an inhibitor against dengue virus and a patent application is imminent. For MERS CoV, there are several promising hits, all from a library of FDA-approved compounds as a spin-off of previous work on the related SARS CoV.

Importantly, several new mouse models have been developed with a variety of viruses. These will enable a much greater level of study of proof of concept through in vivo studies, as the new inhibitors are moved from hits to promising leads.

For crystallography there have been continuous software updates for high-throughput screening of possible target-ligand complexes used ultimately in inhibitor identification. Use of medicinal chemistry, mechanism of action studies, determination of toxicity profiles, proof-of-concept experiments for the most promising molecules and compounds is intensifying lead optimisation.

SILVER activities could result in the discovery of two or more new antiviral molecules or compounds after rigorous proof of concept trials in relevant animal models. Quality of life and economic growth are intimately linked and are frequently seriously affected by emerging viruses. Discovery of safe and effective viral inhibitors will help to alleviate epidemic outbreaks that have an enormous social and economic cost.