Risk factors for liver enzyme elevation with remdesivir use in the treatment of paediatric COVID-19.

AIM: Remdesivir (RDV) causes liver enzyme elevation in adults; however, the frequency of this elevation in children and the associated risk factors are largely unknown. Therefore, we aimed to examine risk factors for liver enzyme elevation in hospitalised paediatric patients who received RDV. METHODS: This was a retrospective case-control study of all patients aged <18 years who were diagnosed with coronavirus disease 2019 and received RDV at a tertiary care hospital between February 2022 and September 2023. Demographic and clinical data were retrieved from the medical records and analysed. Patients with liver enzyme elevation were defined as cases, while those with no liver enzyme elevation were defined as controls. The two groups were compared and analysed for possible risk factors for liver enzyme elevation with RDV use. RESULTS: Sixty-six patients were treated with RDV, 12 (18.2%) of whom developed liver enzyme elevation. Liver enzyme elevation was associated with the median duration of RDV administration (7.5 days vs. 3 days, P = 0.012), median total RDV dose (17.7 mg/kg vs. 10.3 mg/kg, P = 0.017) and acetaminophen use (67% vs. 22%) (odds ratio = 4.34; 95% confidence interval, 1.05-19.97, P = 0.023). All patients showed improvement, except three who had no liver enzyme measurements after having the highest aspartate aminotransferase and alanine aminotransferase values during the observation period. CONCLUSION: Liver enzyme elevation was reversible after discontinuing RDV use. Overall, RDV can be considered safe in children with careful monitoring.

Mutational analyses of Cry protein block7 polypeptides that facilitate the formation of protein inclusion in Escherichia coli.

4AaCter is the polypeptide from the C-terminal extension of mosquitocidal Cry4Aa toxin, and facilitates formation of protein inclusion in Escherichia coli. It has been demonstrated that the use of 4AaCter as a peptide tag results in the efficient production of heterologous protein in E. coli. It has also been demonstrated that proteins are integrated, without losing their biological activities, into the protein inclusions. Although the mechanism to form protein inclusions in E. coli is unclear, highly conserved block7 sequence in 4AaCter is thought to be one of the functional factors. In this study, to analyze the ability of block7 to form protein inclusion, synthetic genes encoding the block7 polypeptide from selected 15 Cry proteins were constructed and expressed to produce glutathione S-transferase fusions in E. coli. Unexpectedly, only three of them (Cry5Ba, Cry32Aa, and Cry48Aa) formed protein inclusion as efficiently as that of Cry4Aa (>90% efficiency). The efficiencies in forming the protein inclusion were ranging from 39% to 66% for most of the tested block7s, and almost no protein inclusion was observed in Cry47Aa block7. This suggested that the ability of block7 to form the protein inclusion may vary with the type of Cry protein or the amino acid sequences. Mutational analyses revealed that substitution of the hydrophobic amino acids in block7 significantly affected the formation of protein inclusion, suggesting some important roles of these hydrophobic amino acid residues. Present results will contribute to develop a compact peptide tag based on block7 which forms the protein inclusion efficiently.