Screening Platform Marseille-Luminy (PCML)

• Bardiot D, Vangeel L, Koukni M, Arzel P, Zwaagstra M, Lyoo H, Wanningen P, Ahmad S, Zhang L, Sun X, Delpal A, Eydoux C, Guillemot JC, Lescrinier E, Klaassen H, Leyssen P, Jochmans D, Castermans K, Hilgenfeld R, Robinson C, Decroly E, Canard B, Snijder EJ, van Hemert MJ, van Kuppeveld F, Chaltin P, Neyts J, De Jonghe S, Marchand A.”Synthesis, Structure-Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication.“Molecules. 2022 Feb 4;27(3):1052.PMID: 35164317
• Shannon A, Fattorini V, Sama B, Selisko B, Feracci M, Falcou C, Gauffre P, El Kazzi P, Delpal A, Decroly E, Alvarez K, Eydoux C, Guillemot JC, Moussa A, Good SS, La Colla P, Lin K, Sommadossi JP, Zhu Y, Yan X, Shi H, Ferron F, Canard B.”A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase.“Nat Commun. 2022 Feb 2;13(1):621.PMID: 35110538
• Lo HS, Hui KPY, Lai HM, He X, Khan KS, Kaur S, Huang J, Li Z, Chan AKN, Cheung HH, Ng KC, Ho JCW, Chen YW, Ma B, Cheung PM, Shin D, Wang K, Lee MH, Selisko B, Eydoux C, Guillemot JC, Canard B, Wu KP, Liang PH, Dikic I, Zuo Z, Chan FKL, Hui DSC, Mok VCT, Wong KB, Mok CKP, Ko H, Aik WS, Chan MCW, Ng WL.”Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.“ACS Cent Sci. 2021 May 26;7(5):792-802.PMID: 34075346
• Eydoux C, Fattorini V, Shannon A, Le TT, Didier B, Canard B, Guillemot JC.”A fluorescence-based high throughput-screening assay for the SARS-CoV RNA synthesis complex.“J Virol Methods. 2021 Feb;288:114013.PMID: 33166547
• Shannon A, Le NT, Selisko B, Eydoux C, Alvarez K, Guillemot JC, Decroly E, Peersen O, Ferron F, Canard B.”Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites.“Antiviral Res. 2020 Jun;178:104793.PMID: 32283108
• Olivon F, Remy S, Grelier G, Apel C, Eydoux C, Guillemot JC, Neyts J, Delang L, Touboul D, Roussi F, Litaudon M.”Antiviral Compounds from Codiaeum peltatum Targeted by a Multi-informative Molecular Networks Approach.“J Nat Prod. 2019 Feb 22;82(2):330-340.PMID: 30681849
• Ferreira-Ramos AS, Li C, Eydoux C, Contreras JM, Morice C, Quérat G, Gigante A, Pérez Pérez MJ, Jung ML, Canard B, Guillemot JC, Decroly E, Coutard B.”Approved drugs screening against the nsP1 capping enzyme of Venezuelan equine encephalitis virus using an immuno-based assay.“Antiviral Res. 2019 Mar;163:59-69.PMID: 30639438
• 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

• European Project IMICARE : Compounds screening and their characterization on the SARS-Coronavirus replicative complex
• REGA Institute, Leuven/Belgium (IMICARE project) : Platting and providing of an industrial library
• Society X : Screening on flaviviruses polymerases and determination of IC50 values on the interest molecules.
• 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.

• 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

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.