The activity and mode of action of the new nucleoside analog (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (2HM-HBG) against varicella-zoster virus (VZV) were determined. In cell culture, replication of different strains of VZV was inhibited to 50% by 0.4 to 0.7 microM 2HM-HBG, while 685 microM was required to inhibit 50% of the DNA synthesis in uninfected human lung fibroblasts. A thymidine kinase-negative VZV strain was not inhibited by 100 microM 2HM-HBG. Inhibition of VZV replication was not reversible after 7 to 14 days of incubation, depending on the multiplicity of VZV. 2HM-HBG was shown to be selectively phosphorylated by purified VZV thymidine kinase, with an inhibition constant of 32.5 microM. The antiviral activity of 2HM-HBG in cell culture was decreased by the addition of deoxythymidine and deoxycytidine but not by other ribo- or deoxyribonucleosides.
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http://dx.doi.org/10.1128/AAC.31.1.76 | DOI Listing |
Anal Chem
January 2025
Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642, China.
The rapid, sensitive, and accurate detection of paralytic shellfish toxins (PSTs), such as saxitoxin (STX), is critical for protecting human health due to the frequent occurrence of toxic red tides. In this work, to address the low affinity of traditional mouse monoclonal antibodies (m-mAbs), rabbit monoclonal antibodies (r-mAbs) against STX were produced by a single B-cell sorting culture and a cross-selection strategy. The r-mAbs showed 100-fold improvement in sensitivity (IC = 0.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
Université de Reims Champagne Ardenne, INRAE, RIBP USC 1488, 51100 Reims, France.
Stilbenes are specialized metabolites that are particularly abundant in species. Although the biosynthetic pathways of stilbenes have been well-characterized, the role of specific peroxidases in stilbene oligomerization remains to be investigated. In this study, we used grapevine cell cultures to characterize the functional role of peroxidase 4 (VvPRX4) in the production of resveratrol oligomers after elicitation with methyl jasmonate (MeJA).
View Article and Find Full Text PDFPLoS Pathog
January 2025
Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, United States of America.
HBV genotype A has two major subtypes, A1 (commonly in Africa) and A2 (commonly in Europe) with only 4% nucleotide differences. Individuals infected with these two subtypes appear to have different clinical manifestations and virologic features. Whether such a difference results from the virus or host has not been established.
View Article and Find Full Text PDFToxicol Sci
January 2025
Takeda Development Center Americas, Inc, Cambridge, MA, USA.
The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.
View Article and Find Full Text PDFMar Biotechnol (NY)
January 2025
Key Laboratory of Mariculture, Ministry of Education (KLMME), Ocean University of China, Qingdao, 266003, China.
Given the challenges of overcrowded coastal aquaculture spaces and insufficient production, utilizing saline-alkaline water areas represents a vital strategy to alleviate these bottlenecks. Spotted sea bass (Lateolabrax maculatus), with its formidable osmoregulatory capabilities, is an ideal candidate to develop a saline-alkaline tolerant strain. In our study, genotypic and phenotypic data from 287 L.
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