CNRS - AIX MARSEILLE UNIV: UMR7257

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Screening Platform Marseille-Luminy (PCML)

Head Jean-Claude GUILLEMOT

The screening facility of Marseille-Luminy (PCML) is linked to several topics in antiviral research and drug design. Our service is highly flexible and allows external users to choose from several research services (collaboration, agreement service,…). PCML offers its expertise and know-how at various levels:

  • Screening inhibitors of proteins and viral enzymes
    • Screening using viral enzymes and biochemical characterization
    • Inhibitor screening of protein-protein or protein-ligand interactions
    • Low-scale high-throughput screening of biochemical assays
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  • Chemical library
    • From library available at AFMB
    • From diversity-oriented library
    • Custom library synthesis and SAR studies
  • Development of new technologies
    • Small-scale assays
    • Fluorescence assays
    • Other assays (e.g., HTRF)
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PCML also offers the possibility to screen for compounds likely to inhibit the catalytic activity of a specific enzyme or to screen for other compounds using our enzyme catalog.

PCML is a partner of the multi-site Antiviral Drug Design Platform (AD2P) facility. This collaborative network, labelled IBISA and Aix-Marseille technological platform, has been launched in 2005 and consists of PCML, the viral screening facility of Marseille-Timone (PCVMT, resp. Gilles Querat) and the Interaction, Dynamics and Drug-design facility (INT-3D, resp. Xavier Morelli). Such a federation of complementary expertise creates a dynamic interface for project development and optimization.

Accessibility

Academics and industrials

Contact

Supply of library, assay development, other services:
Pr. Jean-Claude Guillemot

Specific equipment

  • 1 chemical library made of 65 000 compounds
  • 1 level 2 lab for biochemical experiments with radioactive sources
  • 1 level 2 lab for cell culture experiments
  • 1 liquid handling Beckman I5 equipped with a 96 tips and a 384 tips head
  • 1 liquid handling Beckman 4000 equipped with 1 or 8 tips heads
  • 1 scintillation counter MicroBeta trilux (Perkin Elmer)
  • 1 phospho-imager Amersham Typhoon (Life sciences)
  • 1 PheraStar omega (BMG Labtech)
  • 1 fluorimeter Tecan Safire2
  • 1 LISM

Cost

To be defined from the service requested.

Publications issued from this facility

  • Aouadi W, Eydoux C, Coutard B, Martin B, Debart F, Vasseur JJ, Contreras JM, Morice C, Quérat G, Jung ML, Canard B, Guillemot JC, Decroly E. "Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay." Antiviral Res. 2017 Aug;144:330-339. Epub 2017 Jul 1. PMID: 28676301
  • Milhas S, Raux B, Betzi S, Derviaux C, Roche P, Restouin A, Basse MJ, Rebuffet E, Lugari A, Badol M, Kashyap R, Lissitzky JC, Eydoux C, Hamon V, Gourdel ME, Combes S, Zimmermann P, Aurrand-Lions M, Roux T, Rogers C, Müller S, Knapp S, Trinquet E, Collette Y, Guillemot JC, Morelli X. "Protein-Protein Interaction Inhibition (2P2I)-Oriented Chemical Library Accelerates Hit Discovery." ACS Chem Biol. 2016 Aug 19;11(8):2140-8. Epub 2016 Jun 3. PMID: 27219844
  • Coulerie P, Nour M, Maciuk A, Eydoux C, Guillemot JC, Lebouvier N, Hnawia E, Leblanc K, Lewin G, Canard B, Figadère B. « Structure-activity relationship study of biflavonoids on the Dengue virus polymerase DENV-NS5 RdRp » Planta Med. 2013 Sep;79(14):1313-8. Epub 2013 Aug 8. PMID: 23929244
  • Bourjot M, Leyssen P, Eydoux C, Guillemot JC, Canard B, Rasoanaivo P, Guéritte F, Litaudon M. “Chemical constituents of Anacolosa pervilleana and their antiviral activities”. Fitoterapia. 2012 Sep;83(6):1076-80. Epub 2012 May 14. PMID: 22613073
  • Allard PM, Dau ET, Eydoux C, Guillemot JC, Dumontet V, Poullain C, Canard B, Guéritte F, Litaudon M. “Alkylated Flavanones from the Bark of Cryptocarya chartacea As Dengue Virus NS5 Polymerase Inhibitors.” J Nat Prod. 2011 Nov 28;74(11):2446-53 Epub 2011 November 3 PMID: 22050318
  • Norder H, De Palma AM, Selisko B, Costenaro L, Papageorgiou N, Arnan C, Coutard B, Lantez V, De Lamballerie X, Baronti C, Solà M, Tan J, Neyts J, Canard B, Coll M, Gorbalenya AE, Hilgenfeld R. “Picornavirus non-structural proteins as targets for new anti-virals with broad activity.” Antiviral Res. 2011 Mar;89(3):204-18. Epub 2011 Jan 12. PMID:21236302
  • Massé N, Davidson A, Ferron F, Alvarez K, Jacobs M, Romette JL, Canard B, Guillemot JC. “Dengue virus replicons: production of an interserotypic chimera and cell lines from different species, and establishment of a cell-based fluorescent assay to screen inhibitors, validated by the evaluation of ribavirin’s activity.” Antiviral Res. 2010 Jun;86(3):296-305. Epub 2010 Mar 20. PMID: 20307577
  • Selisko B, Peyrane F, Canard B, Alvarez K, Decroly E. “Biochemical characterization of the (nucleoside-2’O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides 7MeGpppACn and GpppACn” J Gen Virol 2010 Jan;91(Pt 1):112-21. Epub 2009 Sep 23. PMID:19776234
  • Betzi S, Eydoux C, Bussetta C, Blemont M, Leyssen P, Debarnot C, Ben-Rahou M, Haiech J, Hibert M, Gueritte F, Grierson DS, Romette JL, Guillemot JC, Neyts J, Alvarez K, Morelli X, Dutartre H, Canard B. “Identification of allosteric inhibitors blocking the hepatitis C virus polymerase NS5B in the RNA synthesis initiation step.” Antiviral Res. 2009 Oct;84(1):48-59. Epub 2009 Jul 7. PMID: 19589358
  • Hall RA, Tan SE, Selisko B, Slade R, Hobson-Peters J, Canard B, Hughes M, Leung JY, Balmori-Melian E, Hall-Mendelin S, Pham KB, Clark DC, Prow NA, Khromykh AA.“Monoclonal antibodies to the West Nile virus NS5 protein map to linear and conformational epitopes in the methyltransferase and polymerase domains.” J Gen Virol. 2009 Dec;90(Pt 12):2912-22. Epub 2009 Aug 26. PMID:19710254
  • Luzhkov VB, Selisko B, Nordqvist A, Peyrane F, Decroly E, Alvarez K, Karlen A, Canard B, Åqvist J. “Virtual screening and bioassay study of novel inhibitors for dengue virus mRNA cap (nucleoside-2’O)-methyltransferase”. Bioorg Med Chem. 2007 Jul;83(1):28-34. Epub 2009 Mar 14. PMID:19501254
  • Malet H, Massé N, Selisko B, Romette JL, Alvarez K, Guillemot JC, Tolou H, Yap TL, Vasudevan S, Lescar J, Canard B. “The flavivirus polymerase as a target for drug discovery.” Antiviral Res. 2008 Oct;80(1):23-35. Epub 2008 Jul 9. Review. PMID: 18611413
  • Selisko B, Dutartre H, Guillemot JC, Debarnot C, Benarroch D, Khromykh A, Desprès P, Egloff MP, Canard B.“Comparative mechanistic studies of de novo RNA synthesis by flavivirus RNA-dependent RNA polymerases.” Virology. 2006 Jul 20;351(1):145-58. Epub 2006 Apr 21. PMID: 16631221

For more informations...

Service projects :

  • REGA Institute, Leuven/Belgium (SILVER project): providing of chemical library (ChemBridge)
  • AFMB “Structural disorder and molecular recognition: Development and miniaturization of an HTRF assay
  • REGA Institute, Leuven/Belgium: Determination of IC50 values on dengue virus (Flaviviridae) polymerase of potential inhibitors
  • Society X: Screening on Dengue virus polymerase and determination of IC50 values on the interest molecules.
  • Society X: specific assay development on Dengue NS5 and screening.
  • Society Fabre: screening compounds on the methyltransferase of different virus.

Collaborations:

  • Multicentric study, F. Ausseil (CNRS-Fabre), L. Lafanechère (UJF-Grenoble), P. Villa (Strasbourg).
  • Bombay College Of Pharmacy, Mumbai : Screening of potential inhibitor molecules from Bombay College on four in-house methyltransferases (Coronaviridae, Flaviviridae, human).
  • FP7 European Project SILVER (Small-molecule Inhibitor Leads Versus emerging and neglected RNA viruses) : Characterization of several inhibitory molecules on Picornaviridae polymerases (specificity, Ki values, mode of inhibition), characterization of inhibitory molecules on dengue virus polymerase.
  • Institut de Chimie des Substances Naturelles (ICSN), la faculté de Pharmacie UMR 8076 Université Paris-Sud et le LIVE-UNCEA université de Nouvelle Calédonie: Screening of natural extracts and fractions (Bioguided fractionation), discovery of inhibitors of Dengue virus polymerase, biochemical characterization of inhibitors on dengue virus polymerase and specificity towards other virus polymerases, determination of cytotoxicity and inhibitory potency on replicon system.
  • Institut Curie Paris, Institut de chimie des substances naturelles (ICSN) and School of Biotechnology and Pharmacy, Strasbourg within ANR Dengue: Screening of “chimiothèque nationale”, discovery of inhibitors of Dengue virus polymerase, biochemical characterization of inhibitors on dengue virus polymerase and specificity towards other virus polymerases, determination of cytotoxicity and inhibitory potency on replicon system.
  • FP6 European Project VIZIER (Comparative Structural genomics of Viral Enzymes involved in Replication) : Discovery of an inhibitor of dengue virus nucleoside-2’O methyltransferase, screen of molecules on Coxsackie virus B3 polymerase (Picornaviridae)
  • Center for Infectious Desease Research, School of Chemistry and Molecular Biosciences, University of Queensland : test of the inhibitory effect of anti-West-Nile virus NS5 antibodies on polymerase activity.
  • Collaboration with Prestwick Chemical (ANR VMTasIn) : screening of the Prestwick library by HTRF on Dengue and SARS methytransferases.
  • Collaboration with the virology laboratory, biological chemistry department of the exact and natural sciences of the faculty of Buenos Aires, Argentina : Analysis of the inhibitory effect of anti-dengue virus compounds on viral NS5 protein activities

Patents: PCML has a current pattent in valorisation by the SATT-SE (Dengue antivirals: new active chemical entities against the Dengue virus n°EP13305019.5 (20th June 2013)), targeting the 4 serotypes of the Dengue virus and others members of the Flavivirus family, human pathogens, as the Zika virus.

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