" On the one hand, we are developing a safe, middle throughput seroneutralization assay to correlate standard serology to seroneutralization and to enable vaccine response analysis. On the other hand, we develop a basic research project on the identification of a promising drug target site in the RNA-dependent RNA polymerase of positive-stranded RNA viruses, conserved in SARS-CoV-2. During researches performed in the framework of an EOS program, we seredendipitously discovered a conserved region of viral RNA-dependent RNA-polymerases that has properties to be targetable by drugs. This site appears to be conserved in several viruses including SARS-CoV-2 and other important human pathogens. In collaboration with a swiss group working on coronaviruses and other partners, we plan to examine the impact of this polymerase target site on the replication of several viruses, its drugability and the reason for its conservation during evolution. "
Funding: - contribution to a small consortium (lead by Laure Dumoutier) asking for a crédit d'urgence. - the main project will be submitted to the "projets exceptionnels de recherche" call
Publication References: "1. The Importance Of Naturally Attenuated Sars‐Cov‐2 In The Fight Against Covid‐19 Jean Armengaud, Agnès Delaunay‐Moisan, Jean‐Yves Thuret, Eelco van Anken, Diego Acosta‐Alvear, Tomás Aragón, Carolina Arias, Marc Blondel, Ineke Braakman, Jean‐François Collet, René Courcol, Antoine Danchin, Jean‐François Deleuze, Jean‐Philippe Lavigne, Sophie Lucas, Thomas Michiels, Edward RB Moore, Jonathon Nixon‐Abell, Ramon Rossello‐Mora, Zhengli Shi, Antonio G Siccardi, Roberto Sitia, Daniel Tillett, Kenneth N Timmis, Michel B Toledano, Peter van der Sluijs, Elisa Vicenzi Environmental Microbiology, 2020, in press (Opinion on sequencing SARS-CoV-2 strains in asymptomatic patients) 2. The Leader Protein of Theiler's Virus Prevents the Activation of PKR. Borghese F, Sorgeloos F, Cesaro T, Michiels T. J Virol. 2019 Sep 12;93(19):e01010-19. doi: 10.1128/JVI.01010-19. (novel PKR antagonism mechanism) 3. A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L. Drappier M, Jha B.K., Stone S, Elliott R, Zhang R, Vertommen D, Weiss S.R., Silverman R.H., Michiels T. PLoS Pathog. 2018, 4. Evasion of Antiviral Innate Immunity by Theiler's Virus L* Protein through Direct Inhibition of RNase L. Sorgeloos F, Jha BK, Silverman RH, Michiels T. PLoS Pathog. 2013, 9(6):e1003474 (3 & 4): evidence for a novel viral antagonism mechanism of RNase L 5. IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. S. Sommereyns, S. Paul, P. Staeheli, T. Michiels. PLoS Pathog. 2008, 4: e1000017. (first evidence for the main difference between type I and type III interferon activities)."
Thomas Michiels, Professor