First-in-class allosteric inhibitors of bacterial IMPDHs

European Journal of Medicinal Chemistry

Alexandre T, Lupan A, Helynck O, Vichier-Guerre S, Dugué L, Gelin M, Haouz A, Labesse G, Munier-Lehmann H
European Journal of Medicinal Chemistry - vol. 167 124-132 (2019)

Inosine-5‘-monophosphate dehydrogenase (IMPDH) is an essential enzyme in many bacterial pathogens and is considered as a potential drug target for the development of new antibacterial agents. Our recent work has revealed the crucial role of one of the two structural domains (i.e. Bateman domain) in the regulation of the quaternary structure and enzymatic activity of […]

A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects

DMM Disease Models and Mechanisms

Delerue T, Tribouillard-Tanvier D, Daloyau M, Khosrobakhsh F, Emorine LJ, Friocourt G, Belenguer P, Blondel M, Arnauné-Pelloquin L
DMM Disease Models and Mechanisms - vol. 12 1-9 (2019)

Mitochondria continually move, fuse and divide, and these dynamics are essential for the proper function of the organelles. Indeed, the dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs as well as preserving their integrity. As a consequence, mitochondrial fusion and fission dynamics and the […]

Metabolomics-Driven Exploration of the Chemical Drug Space to Predict Combination Antimicrobial Therapies

Molecular Cell

Campos AI, Zampieri M
Molecular Cell - vol. 74 1291-1303.e6 (2019)

Alternative to the conventional search for single-target, single-compound treatments, combination therapies can open entirely new opportunities to fight antibiotic resistance. However, combinatorial complexity prohibits experimental testing of drug combinations on a large scale, and methods to rationally design combination therapies are lagging behind. Here, we developed a combined experimental-computational approach to predict drug-drug interactions using […]

Approved drugs screening against the nsP1 capping enzyme of Venezuelan equine encephalitis virus using an immuno-based assay

Antiviral Research

Ferreira-Ramos AS, Li C, Eydoux C, Contreras JM, Morice C, Quérat G, Gigante A, Pérez Pérez MJ, Jung ML, Canard B, Guillemot JC, Decroly E, Coutard B
Antiviral Research - vol. 163 59-69 (2019)

Alphaviruses such as the Venezuelan equine encephalitis virus (VEEV) are important human emerging pathogens transmitted by mosquitoes. They possess a unique viral mRNA capping mechanism catalyzed by the viral non-structural protein nsP1, which is essential for virus replication. The alphaviruses capping starts by the methylation of a GTP molecule by the N7-guanine methyltransferase (MTase) activity; […]

Identification of Off-Patent Compounds That Present Antifungal Activity against the Emerging Fungal Pathogen Candida auris

Frontiers in Cellular and Infection Microbiology

De Oliveira HC, Monteiro MC, Rossi SA, Pemán J, Ruiz-Gaitán A, Mendes-Giannini MJS, Mellado E, Zaragoza O
Frontiers in Cellular and Infection Microbiology - vol. 9 1-10 (2019)

Candida auris is an emerging fungal pathogen of great concern among the scientific community because it is causing an increasing number of hospital outbreaks of difficult management worldwide. In addition, isolates from this species frequently present reduced susceptibility to azole and echinocandin drugs. For this reason, it is necessary to develop new antifungal strategies to […]

Evaluation of a library of FDA-approved drugs for their ability to potentiate antibiotics against multidrug-resistant gram-negative pathogens

Antimicrobial Agents and Chemotherapy

Hind CK, Dowson CG, Sutton JM, Jackson T, Clifford M, Garner RC, Czaplewski L
Antimicrobial Agents and Chemotherapy - vol. 63 1-6 (2019)

The Prestwick library was screened for antibacterial activity or « antibiotic resistance breaker » (ARB) potential against four species of Gram-negative pathogens. Discounting known antibacterials, the screen identified very few ARB hits, which were strain/drug specific. These ARB hits included antimetabolites (zidovudine, floxuridine, didanosine, and gemcitabine), anthracyclines (daunorubicin, mitoxantrone, and epirubicin), and psychoactive drugs (gabapentin, fluspirilene, and […]

The 2019 Garrod Lecture: MDR efflux in Gram-negative bacteria – How understanding resistance led to a new tool for drug discovery

Journal of Antimicrobial Chemotherapy

Piddock LJ
Journal of Antimicrobial Chemotherapy - vol. 74 3128-3134 (2019)

The AcrAB-TolC MDR efflux system confers intrinsic MDR and overproduction confers clinically relevant resistance to some antibiotics active against Gram-negative bacteria. The system is made up of three components, namely AcrA, AcrB and TolC, otherwise known as the AcrAB-TolC tripartite system. Inactivation or deletion of a gene encoding one of the constituent proteins, or substitution […]

A Small Molecule Targeting Mutagenic Translesion


Wojtaszek JL, Chatterjee N, Najeeb J, Hong J, Walker GC, Zhou P
Cell - vol. 178 152-159.e11 (2019)

Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria


Kanvatirth P JR
PLoS ONE - vol. 14 1-40 (2019)

Clinical validation of blood/brain glutamate grabbing in acute ischemic stroke

Annals of Neurology

da Silva-Candal A, Pérez-Díaz A, Santamaría M, Correa-Paz C, Rodríguez-Yáñez M, Ardá A, Pérez-Mato M, Iglesias-Rey R, Brea J, Azuaje J, Sotelo E, Sobrino T, Loza MI, Castillo J, Campos F
Annals of Neurology - vol. 84 260-273 (2018)

Objective: Blood/brain-glutamate grabbing is an emerging concept in the treatment of acute ischemic stroke, where essentially the deleterious effects of glutamate after ischemia are ameliorated by coaxing glutamate to enter the bloodstream and thus reducing its concentration in the brain. Aiming to demonstrate the clinical efficacy of blood glutamate grabbers in patients with stroke, in […]