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Synthesis, Characterization, Bioavailability and Antimicrobial Studies of Cefuroxime-Based Organic Salts and Ionic Liquids
Publication . Faísca, Francisco; Petrovski, Željko; Grilo, Inês; Lima, Sofia A.C.; Santos, Miguel M.; Branco, Luis C.; DQ - Departamento de Química; LAQV@REQUIMTE; Faculdade de Ciências e Tecnologia (FCT); UCIBIO - Applied Molecular Biosciences Unit; DCV - Departamento de Ciências da Vida; MDPI - Multidisciplinary Digital Publishing Institute
Low oral bioavailability is a common feature in most drugs, including antibiotics, due to low solubility in physiological media and inadequate cell permeability, which may limit their efficacy or restrict their administration in a clinical setting. Cefuroxime is usually administered in its prodrug form, cefuroxime axetil. However, its preparation requires further reaction steps and additional metabolic pathways to be converted into its active form. The combination of Active Pharmaceutical Ingredients (APIs) with biocompatible organic molecules as salts is a viable and documented method to improve the solubility and permeability of a drug. Herein, the preparations of five organic salts of cefuroxime as an anion with enhanced physicochemical characteristics have been reported. These were prepared via buffer-assisted neutralization methodology with pyridinium and imidazolium cations in quantitative yields and presented as solids at room temperature. Cell viability studies on 3T3 cells showed that only the cefuroxime salts combined with longer alkyl chain cations possess higher cytotoxicity than the original drug, and while most salts lost in vitro antibacterial activity against E. coli, P. aeruginosa and B. subtilis, one compound, [PyC10Py][CFX]2, retained the activity. Cefuroxime organic salts have a water solubility 8-to-200-times greater than the original drug at 37 °C. The most soluble compounds have a very low octanol-water partition, similar to cefuroxime, while more lipophilic salts partition predominantly to the organic phase.
Detection and Prevalence of Coronaviruses in European Bats
Publication . Hemnani, Mahima; da Silva, Priscilla Gomes; Thompson, Gertrude; Poeta, Patrícia; Rebelo, Hugo; Mesquita, João R.; LAQV@REQUIMTE; Springer
Bats are known hosts for a wide range of coronaviruses (CoVs), including those that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV). With the emergence of the COVID-19 pandemic caused by the SARS-CoV-2 virus, it has become increasingly important to understand the diversity and prevalence of CoVs in bat populations. This systematic review aimed to compile studies that have sampled CoVs from bats across Europe and assessed various aspects related to the testing of bat samples, including the country where the bats were collected, the CoV genomic region studied, the CoV genera that were detected, and the identification of bat species that were found to be carrying CoV. We identified 30 studies that assessed CoVs presence in bats across multiple countries including Italy, Germany, and various other nations with one or two studies each, which tested them for CoVs using a variety of matrices. CoVs were found in nine genera of bats, and the genomic regions included RdRp, ORF1a gene, as well as full genome, detecting α- and/or β-CoVs, with most of them being detectable only in faeces. This review provides a comprehensive overview of the CoVs detected in bats across Europe and highlights the importance of continued surveillance and monitoring of bat populations for potential emerging zoonotic CoVs.
Metagenomic analysis of viral diversity in Portuguese bats
Publication . Hemnani, Mahima; Karatas, Mustafa; Cruz, Andreia V. S.; Silva, Priscilla Gomes da; Thompson, Gertrude; Poeta, Patrícia; Rebelo, Hugo; Matthijnssens, Jelle; Mesquita, João R.; LAQV@REQUIMTE; DQ - Departamento de Química; Springer Science and Business Media B.V.
Bats are highly diverse mammals and known reservoirs of numerous zoonotic viruses. Their role in the ecology of emerging infectious diseases continues to be of significant interest. This study aimed to evaluate the occurrence of coronaviruses (CoVs) in Portuguese bats and predict the affinity of their spike proteins with the aminopeptidase N (APN) receptor of several host species. The study also explored the viral diversity in bat samples using metagenomic sequencing. Ten bats (five Myotis myotis and five Miniopterus schreibersii) were captured at an underground roost in 2022 (Central Portugal), and fecal samples, oral, and anal swabs were collected (n = 27). A Pan-CoV nested RT-PCR was used for initial screening, followed by viral metagenomic sequencing of all fecal samples and one CoV-positive buccal swab. In silico protein docking studies were performed between a Portuguese bat CoV spike protein and APNs of bats, pigs, and humans. Pan-CoV nested RT-PCR identified three positive samples: two fecal samples and one buccal sample. Metagenomic sequencing allowed us to determine two near complete CoV genomes. Protein docking predicted strong binding of this spike protein to bat, porcine, and human APN receptors. Metagenomics also identified picornaviruses, adenovirus, and dependoparvovirus in fecal samples. This study reports the first near complete genome sequences of two members of the Alphacoronavirus genus from a Portuguese bat The identification of other viral families highlights the diverse virome of these cave-dwelling bat species. Protein docking studies suggest a potential for cross-species transmission of this bat CoV between bats, porcines and humans, though further research is needed to confirm these interactions.
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Fundação para a Ciência e a Tecnologia
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Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
Número da atribuição
UIDP/00772/2020