Synthesis of novel neuraminidase inhibitor -- carborane ester of oseltamivir carboxylic acid is described, and its physicochemical and spectral characteristics is provided. Surprisingly, carborane analog of oseltamivir is of an order of magnitude less active than its precursor, the corresponding ethyl ester, which is the active principle of pharmaceutical preparations used in influenza prophylactics and therapy.
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Subcell Biochem
December 2024
Department of Biomedical Sciences, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
During the last forty years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs eradicating hepatitis C virus infection. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry, or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by means of computer-based approaches.
View Article and Find Full Text PDFViruses
November 2024
Institute for Health and Sport, Immunology and Translational Research Group, Victoria University, Werribee, Melbourne, VIC 3030, Australia.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, Taiwan, ROC; Graduate Institute of Biodefense, National Defense Medical Center, Taipei 11490, Taiwan, ROC. Electronic address:
This study introduced a novel antiviral approach by combining three substances with different antiviral mechanisms: N-(2-hydroxy)propyl-3-trimethylammoniumchitosan (HTC), silver nanoparticles (AgNPs), and oseltamivir. First, positively surface-charged AgNPs were prepared using an environmentally friendly method. The surfaces of these AgNPs were capped with cationic quaternary chitosan HTC.
View Article and Find Full Text PDFBioorg Med Chem Lett
February 2025
Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address:
We reported earlier that oseltamivir (Osm, Tamiflu®), an anti-viral agent, inhibits the attachment of trophozoites to intestinal epithelial cells and cyst production in culture. Osm also disassembles lipid rafts (LRs) and the biogenesis of extracellular vesicles (EVs) by Giardia. In the current study, we synthesized forty-one Osm analogs with the derivatization of oseltamivir phosphate.
View Article and Find Full Text PDFAntiviral Res
December 2024
Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka-shi, Shizuoka, 422-8526, Japan.
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