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Virus adaptation to heparan sulfate comes with capsid stability tradeoff.
Elife
December 2024
Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
Because of high mutation rates, viruses constantly adapt to new environments. When propagated in cell lines, certain viruses acquire positively charged amino acids on their surface proteins, enabling them to utilize negatively charged heparan sulfate (HS) as an attachment receptor. In this study, we used enterovirus A71 (EV-A71) as model and demonstrated that unlike the parental MP4 variant, the cell-adapted strong HS-binder MP4-97R/167G does not require acidification for uncoating and releases its genome in the neutral or weakly acidic environment of early endosomes.
View Article and Find Full Text PDFOptimization of Clozapine Treatment: Study of Variables Affecting Response in Uruguayan Patients With Schizophrenia.
J Clin Psychopharmacol
December 2024
Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo.
Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.
View Article and Find Full Text PDFAcross-the-board review on Omicron SARS-CoV-2 variant.
Inflammopharmacology
December 2024
Department of Pharmacy, Integral University, Lucknow, 226026, India.
Introduction: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a cataclysmic pandemic. Several SARS-CoV-2 mutations have been found and reported since the COVID-19 pandemic began. After the Alpha, Beta, Gamma, and Delta variants, the Omicron (B.
View Article and Find Full Text PDFAssessing the predicted impact of single amino acid substitutions in calmodulin for CAGI6 challenges.
Hum Genet
December 2024
Department of Pharmacy and Biotechnology, University of Bologna, 40126, Bologna, Italy.
Recent thermodynamic and functional studies have been conducted to evaluate the impact of amino acid substitutions on Calmodulin (CaM). The Critical Assessment of Genome Interpretation (CAGI) data provider at University of Verona (Italy) measured the melting temperature (T) and the percentage of unfolding (%unfold) of a set of CaM variants (CaM challenge dataset). Thermodynamic measurements for the equilibrium unfolding of CaM were obtained by monitoring far-UV Circular Dichroism as a function of temperature.
View Article and Find Full Text PDFCefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 coresident plasmids: pKpQIL, carrying variants of bla carbapenemase gene, and pKPN, carrying the ferric citrate transport (FEC) system.
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