CV Science

Bruno Villoutreix Structural bioinformatics and AI-powered drug design

Course and current status

Bruno Villoutreix is research director at INSERM (DR1), the French National Institute of Health and Medical Research.
He has been working at the interface between molecular medicine (mainly cancer, the complement system and blood coagulation), structural bioinformatics and chemoinformatics/AI for over 25 years in different countries (private and academic sectors). He has contributed strongly to the development several chemical probes (small molecules and peptides) with one molecule designed in silico presently in clinical trials. He also worked on the development of more stable therapeutic proteins, on the optimization of monoclonal antibodies and on small molecule drug repositioning. With several collaborators, he developed several software packages and databases that are used worldwide.  

He presently works on the modulation of protein-protein interactions with various types of binders (small molecules, peptides, proteins), on virtual screening and the analysis of point mutations identified in patients. The emphasis is to use various in silico approaches including machine learning to help the development of chemical probes and to assist in the understanding of molecular mechanisms in the health and disease state.

Since Sept 2020: INSERM UMR 1141 - Robert-Debré Hospital - Paris  

Scientific summary

Over 240 publications - Google Scholar H-index 63 (about 14.000 citations) - 15 patents

Villoutreix's research presently focuses on challenging targets (including protein-membrane interactions, protein-protein interactions), the development of AI/machine learning tools for ADME-Tox predictions and rational drug design.

With several colleagues we developed:

a) an online ADME-tox filtering tools: FAF-Drugs (between 15000 to 30000 connections each year)

b) FastTargetPred: tool for target profiling

c) The online virtual screening MTiOpenScreen tool (about 10000 connections each year).

Some selected publications/reviews:

1. Virard F, Giraud S, Bonnet M, Magadoux L, Martin L, Pham TH, Skafi N, Deneuve S, Frem R, Villoutreix BO, Sleiman NH, Reboulet J, Merabet S, Chaptal V, Chaveroux C, Hussein N, Aznar N, Fenouil T, Treilleux I, Saintigny P, Ansieau S, Manié S, Lebecque S, Renno T, Coste I. Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death. Nat Commun. 2024
2. Pernot S, Tomé M, Galeano-Otero I, Evrard S, Badiola I, Delom F, Fessart D, Smani T, Siegfried G, Villoutreix BO, Khatib AM. Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-κB and calcium activity repression. Front Immunol. 2024
3. Singh N, Chaput L, Villoutreix BO. Fast Rescoring Protocols to Improve the Performance of Structure-Based Virtual Screening Performed on Protein-Protein Interfaces. J Chem Inf Model. 2020 Aug 24;60(8):3910-3934.
4. Singh N, Chaput L, Villoutreix BO. Virtual screening web servers: designing chemical probes and drug candidates in the cyberspace. Brief Bioinform. 2021 Mar 22;22(2):1790-1818.
5. Villoutreix BO, Calvez V, Marcelin AG, Khatib A-M. In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2-Spike RBD Interface. Int J Mol Sci. 2021 Feb 8;22(4):1695.
6. Habault J, Thonnart N, Pasquereau-Kotula E, Bagot M, Bensussan A, Villoutreix BO, Marie-Cardine A, Poyet JL. PAK1-Dependent Antitumor Effect of AAC-11‒Derived Peptides on Sézary Syndrome Malignant CD4+ T Lymphocytes. J Invest Dermatol. 2021
7. Gyulkhandanyan A, Rezaie AR, Roumenina L, Lagarde N, Fremeaux-Bacchi V, Miteva MA, Villoutreix BO. Analysis of protein missense alterations by combining sequence- and structure-based methods. Mol Genet Genomic Med. 2020 Apr;8(4):e1166.
8. Villoutreix BO, Beaune PH, Tamouza R, Krishnamoorthy R, Leboyer M. Prevention of COVID-19 by drug repurposing: rationale from drugs prescribed for mental disorders. Drug Discov Today. 2020 Aug;25(8):1287-1290.
9. Soulet F, Bodineau C, Hooks KB, Descarpentrie J, Alves I, Dubreuil M, Mouchard A, Eugenie M, Hoepffner JL, López JJ, Rosado JA, Soubeyran I, Tomé M, Durán RV, Nikolski M, Villoutreix BO, Evrard S, Siegfried G, Khatib AM. ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation. JCI Insight. 2020 Jul 23;5(14):e129070.
10. Nougarede A, Popgeorgiev N, Kassem L, Omarjee S, Borel S, Mikaelian I, Lopez J, Gadet R, Marcillat O, Treilleux I, Villoutreix BO, Rimokh R, Gillet G. Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10. Cancer Res. 2018 Mar 15;78(6):1404-1417.
11. Louet M, Bitam S, Bakouh N, Bignon Y, Planelles G, Lagorce D, Miteva MA, Eladari D, Teulon J, Villoutreix BO. In silico model of the human ClC-Kb chloride channel: pore mapping, biostructural pathology and drug screening. Sci Rep. 2017 Aug 3;7(1):7249.
12. Lagorce D, Bouslama L, Becot J, Miteva MA, Villoutreix BO. FAF-Drugs4: free ADME-tox filtering computations for chemical biology and early stages drug discovery. Bioinformatics. 2017 Nov 15;33(22):3658-3660.
13. Labbé CM, Kuenemann MA, Zarzycka B, Vriend G, Nicolaes GA, Lagorce D, Miteva MA, Villoutreix BO, Sperandio O. iPPI-DB: an online database of modulators of protein-protein interactions. Nucleic Acids Res. 2016 Jan 4;44(D1):D542-7.
14. Nicolaes GA, Kulharia M, Voorberg J, Kaijen PH, Wroblewska A, Wielders S, Schrijver R, Sperandio O, Villoutreix BO. Rational design of small molecules targeting the C2 domain of coagulation factor VIII. Blood. 2014 Jan 2;123(1):113-20
15. Segers K, Sperandio O, Sack M, Fischer R, Miteva MA, Rosing J, Nicolaes GA, Villoutreix BO. Design of protein membrane interaction inhibitors by virtual ligand screening, proof of concept with the C2 domain of factor V. Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12697-702.