Publications


Publications
Exploring the Human Cytomegalovirus Core Nuclear Egress Complex as a Novel Antiviral Target: A New Type of Small Molecule Inhibitors

Alkhashrom S, Kicuntod J, Häge S, Schweininger J, Muller YA, Lischka P, Marschall M, Eichler J.
Viruses 471 (2021)

Nuclear egress is an essential process in the replication of human cytomegalovirus (HCMV), as it enables the migration of newly formed viral capsids from the nucleus into the cytoplasm. Inhibition of the HCMV core nuclear egress complex (core NEC), composed of viral proteins pUL50 and pUL53, has been proposed as a potential new target for […]

Publications
A fluorescence-based high throughput-screening assay for the SARS-CoV RNA synthesis complex

Journal of Virological Methods

Eydoux C, Fattorini V, Shannon A, Le TTN, Didier B, Canard B, Guillemot JC
Journal of Virological Methods - vol. 288 114013 (2021)

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) emergence in 2003 introduced the first serious human coronavirus pathogen to an unprepared world. To control emerging viruses, existing successful anti(retro)viral therapies can inspire antiviral strategies, as conserved viral enzymes (eg., viral proteases and RNA-dependent RNA polymerases) represent targets of choice. Since 2003, much effort has been expended […]

Publications
Quantitative Automated Assays in Living Cells to Screen for Inhibitors of Hemichannel Function

SLAS Discovery

Soleilhac E, Comte M, da Costa A, Barette C, Picoli C, Mortier M, Aubry L, Mouthon F, Fauvarque MO, Charvériat M
SLAS Discovery 1-8 (2020)

In vertebrates, intercellular communication is largely mediated by connexins (Cx), a family of structurally related transmembrane proteins that assemble to form hemichannels (HCs) at the plasma membrane. HCs are upregulated in different brain disorders and represent innovative therapeutic targets. Identifying modulators of Cx-based HCs is of great interest to better understand their function and define […]

Publications
High-Throughput Image-Based Aggresome Quantification

SLAS Discovery

Lesire L, Chaput L, Cruz De Casas P, Rousseau F, Piveteau C, Dumont J, Pointu D, Déprez B, Leroux F
SLAS Discovery 1-9 (2020)

Aggresomes are subcellular perinuclear structures where misfolded proteins accumulate by retrograde transport on microtubules. Different methods are available to monitor aggresome formation, but they are often laborious, time-consuming, and not quantitative. Proteostat is a red fluorescent molecular rotor dye, which becomes brightly fluorescent when it binds to protein aggregates. As this reagent was previously validated […]

Publications
Inhibition of Tryptophan Hydroxylases and Monoamine Oxidase-A by the Proton Pump Inhibitor, Omeprazole—In Vitro and In Vivo Investigations

Frontiers in Pharmacology

Betari N, Sahlholm K, Morató X, Godoy-Marín H, Jáuregui O, Teigen K, Ciruela F, Haavik J
Frontiers in Pharmacology - vol. 11 1-15 (2020)

Serotonin (5-HT) is a hormone and neurotransmitter that modulates neural activity as well as a wide range of other physiological processes including cardiovascular function, bowel motility, and platelet aggregation. 5-HT synthesis is catalyzed by tryptophan hydroxylase (TPH) which exists as two distinct isoforms; TPH1 and TPH2, which are responsible for peripheral and central 5-HT, respectively. […]

Publications
Identification of cardiac glycosides as novel inhibitors of eif4a1-mediated translation in triple-negative breast cancer cells

Cancers

Howard CM, Estrada M, Terrero D, Tiwari AK, Raman D
Cancers - vol. 12 1-18 (2020)

The eukaryotic translation initiation factor 4F complex (eIF4F) is a potential chemotherapeutic target in triple-negative breast cancer (TNBC). This complex regulates cap-dependent translational initiation and consists of three core proteins: eIF4E, eIF4G, and eIF4A1. In this study, we focus on repositioning compounds as novel inhibitors of eIF4A1-mediated translation. In order to accomplish this goal, a […]

Publications
In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication

bioRxiv

Touret F, Gilles M, Barral K, Nougairède A, Decroly E, Lamballerie XD, Coutard B
bioRxiv 2020.04.03.023846 (2020)

A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the […]

Publications
An Unbiased Drug Screen for Seizure Suppressors in Duplication 15q Syndrome Reveals 5-HT1A and Dopamine Pathway Activation as Potential Therapies

Biological Psychiatry

Roy B, Han J, Hope KA, Peters TL, Palmer G, Reiter LT
Biological Psychiatry 1-12 (2020)

Background: Duplication 15q (Dup15q) syndrome is a rare neurogenetic disorder characterized by autism and pharmacoresistant epilepsy. Most individuals with isodicentric duplications have been on multiple medications to control seizures. We recently developed a model of Dup15q in Drosophila by elevating levels of fly Dube3a in glial cells using repo-GAL4, not neurons. In contrast to other […]

Publications
Identification of SARS-CoV-2 Inhibitors using Lung and Colonic Organoids

Nature

Han Y, Duan X, Yang L, Nilsson-Payant BE, Wang P, Duan F, Tang X, Yaron TM, Zhang T, Uhl S, Bram Y, Richardson C, Zhu J, Zhao Z, Redmond D, Houghton S, Nguyen DHT, Xu D, Wang X, Jessurun J, Borczuk A, Huang Y, Johnson JL, Liu Y, Xiang J, Wang H, Cantley LC, tenOever BR, Ho DD, Pan FC, Evans T, Chen HJ, Schwartz RE, Chen S
Nature - vol. 589 (2020)

There is an urgent need to create novel models using human disease-relevant cells to study SARS-CoV-2 biology and to facilitate drug screening. As SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs). The hPSC-LOs, particularly alveolar type II-like cells, are permissive to SARS-CoV-2 infection, and showed […]

Publications
A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus

Nature Scientific Data

Georgi F, Kuttler F, Murer L, Andriasyan V, Witte R, Yakimovich A, Turcatti G, Greber UF
Nature Scientific Data - vol. 7 1-12 (2020)

Human adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny and second-round infections. We analysed 1,280 small molecular weight compounds of the Prestwick Chemical Library (PCL) […]