Bruno Villoutreix Structural bioinformatics and in silico 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 (USA, Finland, Sweden, Bulgaria, France), in the 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 phase II. He also worked on the development of more stable therapeutic proteins in the field of blood coagulation, on the optimization of monoclonal antibodies in the field of cancer and on small molecule drug repositioning with applications in several therapeutic areas. With several collaborators, he developed several software packages and databases.  

He presently works on the modulation of protein-protein interactions with various types of binders (small molecules, peptides, therapeutic proteins), the identification of novel targets and pathways, the use of binding exosites to modulate biological pathways, on in silico ADME-Tox prediction, drug repositioning, point mutations identified in patients. The emphasis is to develop drug candidates by integrating in silico, in vitro and in vivo approaches.

He maintains a repository of in silico tools and databases that assist the early stages of drug discovery (vls3d.com) since 2006 (about 1 million visitors worldwide). He is the co-founder of Akttyva Therapeutics, a company developing targeted therapeutics for vascular barrier disorders, Greater Boston, USA. He owns stock in WNTresearch, a cancer research company located in Sweden. He has been nominated Editor in Chief of Frontiers in Drug Discovery in 2021.

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

Jan 2019 - Aug 2020: Inserm U1177 Lille. Program "Region Hauts de France STaRS – i-Site" : « Accueil de chercheurs statutaires de haut niveau »

Jan 2009-Dec 2018: Founder and director of Inserm-Univ Paris Diderot UMRS-973, Molécules Thérapeutiques in silico (~30 people, in silico Drug discovery, chemoinformatics, Bioinformatics and applications in several therapeutic areas)

From Sept 2012 to Sept 2015: Co-director doctoral school: Medicinal Chemistry, Toxicity, Environment (MTCE, presently MTCi)

2002-2008: Head of the Inserm Avenir team (Bioinformatics, Chemoinformatics, Blood coagulation & Complement)

2005: Research Director Inserm, U648, Univ Paris Descartes (Medicinal chemistry)

2001: Research Director Inserm, U428, Univ Paris Descartes (Blood coagulation disorders)

1998-2001: Associate Professor, Malmo University Hospital, Sweden (Blood coagulation disorders).

1998-2001: Visiting Professor University of Paris 5, School of Pharmacy.

1996-1997: Visiting scientist Structural Bioinformatics, Malmo University Hospital, Sweden (Blood coagulation & Complement).

1995-1996: Visiting scientist Structural Bioinformatics – Drug Design, VTT Biotechnology, Helsinki, Finland. Biologics, diagnostic kits, cancer

1991-1995: Research Assistant Structural Bioinformatics, Scripps Clinic & Research Institute, San Diego, USA (Blood coagulation, complement, cancer).

1991: Student training, Electrostatics (3 months) Central Laboratory of Biophysics, Sofia Bulgaria.

1990-1991: Student training, Structural Bioinformatics, Uppsala, Sweden.

1988 and 1990: visiting scientist: enzyme fast kinetics (5 months). Penn State University, USA.

Scientific summary

Over 240 publications - Google Scholar H-index 56 (about 10.000 citations) - 10 patents - 1 molecule in phase II

Villoutreix's research presently focuses on challenging targets (including protein-membrane interactions, protein-protein interactions) and investigation of novel disease pathways, and on the development of AI/machine learning tools for ADME-Tox predictions and rational drug design (faster identification of hits, hit2lead, drug repositioning, data mining/knowledge discovery/knowledge graphs, multi-parameter optimization, ultra-large screening, in silico 360-degree assessment to speed-up drug discovery and development).

My directory of weblinks dedicated to in silico methods that assist the early steps of drug discovery: http://www.vls3d.com

With several colleagues we developed:

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

b) FastTargetPred: tool for target profiling (with links to biological pathways) and drug repositioning/polypharmacology

c) The online virtual screening MTiOpenScreen tool (about 10000 connections each year) with recent updates involving 3 new collections of purchasable compounds  ready for docking (drug compounds for repositioning, natural products and food-derived products). This tool has been used extensively for drug repositioning studies by many teams around the world during the Covid-19 crisis.

Co-founder of 3 start-ups (France, Sweden and USA)

Some selected publications/reviews:

1. Villoutreix BO. Field Grand Challenge. Post-Pandemic Drug Discovery and Development: Facing Present and Future Challenges. Front. Drug. Discov., 28 July 2021. https://www.frontiersin.org/articles/10.3389/fddsv.2021.728469/full
2. Singh N, Villoutreix BO. Resources and computational strategies to advance small molecule SARS-CoV-2 discovery: Lessons from the pandemic and preparing for future health crises. Comput Struct Biotechnol J. 2021;19:2537-2548.
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. Nature 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.


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