Publications (2018-2020) Toxic Colors : The Use of Deep Learning for Predicting Toxicity of Compounds Merely from Their Graphic Images Introduction The discovery of new chemicals and materials plays a key role in technological innovation and.
Fernandez, M. et al.
ACS publications (2018)
The majority of computational methods for predicting toxicity of chemicals are typically based on “nonmechanistic” cheminformatics solutions, relying on an arsenal of QSAR descriptors, often vaguely associated with chemical structures, and typically employing “black-box” mathematical algorithms. Nonetheless, such machine learning models, while having lower generalization capacity and interpretability, typically achieve a very high accuracy in […]
Publications (2018-2020) Screening a Repurposing Library for Inhibitors of Multidrug-Resistant Candida auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development.
Gina Wall, Ashok K. Chaturvedi, Floyd L. Wormley, Jr., Nathan P. Wiederhold, Hoja P. Patterson, Thomas F. Patterson, J. L. L.-R.
Antimicrob. Agents Chemother (2018)
Since its original isolation in 2009, Candida auris has spread across the globe as a causative agent of invasive candidiasis. C. auris is typically intrinsically resistant to fluconazole and can also be resistant to echinocandins and even amphotericin B. Thus, there is an urgent need to find new treatment options against this emerging pathogen. To address this growing problem, […]
Publications (2018-2020) Blocking fatty acid-fueled mROS production within macrophages alleviates acute gouty inflammation
Hall, C. J. et al.
J. Clin. Invest. 128 1752–1771 (2018)
Gout is the most common inflammatory arthritis affecting men. Acute gouty inflammation is triggered by monosodium urate (MSU) crystal deposition in and around joints that activates macrophages into a proinflammatory state, resulting in neutrophil recruitment. A complete understanding of how MSU crystals activate macrophages in vivo has been difficult because of limitations of live imaging […]
Publications (2018-2020) Extensive impact of non-antibiotic drugs on human gut bacteria.
Maier, L. et al.
Nature 555 623–628 (2018e-10004024)
A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited […]
Clinical validation of blood/brain glutamate grabbing in acute ischemic strokeIl y a 1 mois
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 […]
Publications (2018-2020) Discovery of small molecule inhibitors of adenovirus by disrupting E3-19K/HLA-A2 interactions
Ren, J. et al.
Bioorganic Med. Chem. Lett. 28 2837–2841 (2018)
The binding of the adenovirus (Ad) protein E3-19K with the human leukocyte antigen (HLA) plays an important role in Ad infections, which is the causative agent of a series of gastrointestinal, respiratory and ocular diseases. The objective of this research is to evaluate the essential interactions between E3-19K and HLA-A2 using the X-ray crystal structure […]
Publications (2018-2020) Approved drugs screening against the nsP1 capping enzyme of Venezuelan equine encephalitis virus using an immuno-based assay.
Ferreira-Ramos, A. S. et al.
Antiviral Res. 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; […]
Publications (2018-2020) A Small Molecule Targeting Mutagenic Translesion.
Wojtaszek, J. L. et al.
Cell 178 152-159.e11 (2019)
Intrinsic and acquired drug resistance and induction of secondary malignancies limit successful chemotherapy. Because mutagenic translesion synthesis (TLS) contributes to chemoresistance as well as treatment-induced mutations, targeting TLS is an attractive avenue for improving chemotherapeutics. However, development of small molecules with high specificity and in vivo efficacy for mutagenic TLS has been challenging. Here, we […]
Publications (2018-2020) The 2019 Garrod Lecture: MDR efflux in Gram-negative bacteria – How understanding resistance led to a new tool for drug discovery.
Piddock, L. J. V.
J. Antimicrob. Chemother. 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 […]
Publications (2018-2020) A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects.
Delerue, T. et al.
DMM Dis. Model. Mech. 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 […]