Gerardo Turcatti

Senior scientific level (R&D) with extensive experience in the management of multidisciplinary technological projects. Prof. Gerardo Turcatti, directs the academic technological platform, Biomolecular Screening Facility (BSF) at the EPFL he created in 2006. In the framework of the NCCR-Chemical Biology, he is project leader of the program ACCESS (An Academic Chemical Screening Platform for Switzerland). Previously he co-founded and acted as CTO of Manteia S.A., a Swiss-based company that developed high throughput DNA sequencing technologies currently owned by Illumina and used in the ‘Next Generation Sequencing’ instruments. Prior to this experience, Prof. Turcatti had a long multidisciplinary career in R&D divisions of Biotechnology and Pharmaceutical companies with extensive expertise in several Chemical Biology-related disciplines such as Drug Screening, Chemical Biology, Bio-analytical Chemistry, DNA and Protein Chemistry. Prof. Turcatti earned his Master in Chemical Engineering at the University of Geneva and his PhD in Chemistry and Biochemistry from the EPFL where he received the award for the best doctoral thesis of the year.

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Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitr

A nucleic acid sequence is a succession of bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five diffe

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In prot

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BIOENG-512: Lab methods : bioactive compounds screening

Introduction to the key principles and concepts underlying the screening activity to identify and to characterize bioactive compounds (chemicals, compounds, siRNAs and natural products) acting on a given biological target or a signalling pathway.

BIOENG-518: Methods: from disease models to therapy

This course will describe methods underlying translational approaches from disease modeling and characterization to therapeutic applications. The presented techniques will be complemented by hands-on rotations in the technological platforms of the School of Life Sciences.

ELSEVIER SCIENCE INC2023

High-content, arrayed compound screens with rhinovirus, influenza A virus and herpes simplex virus infections

Fabien Kuttler, Gerardo Turcatti

Viruses are genetically and structurally diverse, and outnumber cells by orders of magnitude. They can cause acute and chronic infections, suppress, or exacerbate immunity, or dysregulate survival and growth of cells. To identify chemical agents with pro- or antiviral effects we conducted arrayed high-content image-based multi-cycle infection screens of 1,280 mainly FDA-approved compounds with three human viruses, rhinovirus (RV), influenza A virus (IAV), and herpes simplex virus (HSV) differing in genome organization, composition, presence of an envelope, and tropism. Based on Z’-factors assessing screening quality and Z-scores ranking individual compounds, we identified potent inhibitors and enhancers of infection: the RNA mutagen 5-Azacytidine against RV-A16; the broad-spectrum antimycotic drug Clotrimazole inhibiting IAV-WSN; the chemotherapeutic agent Raltitrexed blocking HSV-1; and Clobetasol enhancing HSV-1. Remarkably, the topical antiseptic compound Aminacrine, which is clinically used against bacterial and fungal agents, inhibited all three viruses. Our data underscore the versatility and potency of image-based, full cycle virus propagation assays in cell-based screenings for antiviral agents.

2022

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern

Michael Bauer, Fabien Kuttler, Gerardo Turcatti, Liliane Yang

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with oral availability. Methylene blue (MB, used for the treatment of methemoglobinemia), Mycophenolic acid (MPA, used in organ transplantation) and the anti-fungal agent Posaconazole (POS) had the broadest anti-CoV spectrum. They inhibited the shedding of SARS-CoV-2 and variants-of-concern (alpha, beta, gamma, delta) from HAEEC in either pre- or post exposure regimens at clinically relevant concentrations. Co-treatment of cultured cells with MB and the FDA-approved SARS-CoV-2 RNA-polymerase inhibitor Remdesivir reduced the effective anti-viral concentrations of MB by 2-fold, and Remdesivir by 4 to 10-fold, indicated by BLISS independence synergy modelling. Neither MB, nor MPA, nor POS affected the cell delivery of SARS-CoV-2 or OC43 (+)sense RNA, but blocked subsequent viral RNA accumulation in cells. Unlike Remdesivir, MB, MPA or POS did not reduce the release of viral RNA in post exposure regimen, thus indicating infection inhibition at a post-replicating step as well. In summary, the data emphasize the power of unbiased, full cycle compound screens to identify and repurpose broadly acting drugs against coronaviruses.

2022

Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitr

A nucleic acid sequence is a succession of bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five diffe

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In prot

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