Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential.
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http://dx.doi.org/10.1086/522609 | DOI Listing |
BMC Genomics
December 2024
The Key Lab of Animal Disease and Public Health / Luoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Henan University of Science and Technology, Luoyang, Henan, 471023, China.
The H3 subtype of avian influenza virus (AIV) stands out as one of the most prevalent subtypes, posing a significant threat to public health. In this study, a novel triple-reassortant H3N3 AIV designated A/chicken/China/16/2023 (H3N3), was isolated from a sick chicken in northern China. The complete genome of the isolate was determined using next-generation sequencing, and the AIV-like particles were confirmed via transmission electron microscopy.
View Article and Find Full Text PDFVirus Evol
December 2024
Department of Biology, Memorial University of Newfoundland, St. John's, NL A1C 5S7, Canada.
Wild birds are important hosts of influenza A viruses (IAVs) and play an important role in their ecology. The emergence of the A/goose/Guangdong/1/1996 H5N1 (Gs/GD) lineage marked a shift in IAV ecology, leading to recurrent outbreaks and mortality in wild birds from 2002 onwards. This lineage has evolved and diversified over time, with a recent important derivative being the 2.
View Article and Find Full Text PDFFukushima J Med Sci
December 2024
Department of Pediatrics, Fukushima Medical University.
Since 2000, rapid antigen detection kits and anti-influenza drugs have been used for the early diagnosis and treatment of influenza in Japan, respectively. The main drugs available in clinical practice are the neuraminidase inhibitors oseltamivir, zanamivir, laninamivir, and peramivir, as well as the cap-dependent endonuclease inhibitor baloxavir marboxil. Antiviral therapy with neuraminidase inhibitors has been practiced for many years, especially in Japan; it can shorten the febrile period and reduce complications.
View Article and Find Full Text PDFMolecules
November 2024
Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks.
View Article and Find Full Text PDFJ Med Chem
December 2024
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong 250012, P. R. China.
Inspired by our previous finding that targeting the 150-cavity with a multisite-binding strategy emerged as an effective approach to obtain more potent and selective neuraminidase (NA) inhibitors against influenza virus, we present here the design, synthesis, and optimization of novel boron-containing N-substituted oseltamivir (OSC) derivatives. Exploratory structure-activity relationship (SAR) studies led to the identification of compounds and as the most potent NA inhibitors, surpassing OSC in potency against both wild-type group-1 NAs and oseltamivir-resistant NAs. These compounds demonstrated significant antiviral activity against several wild-type strains and H1N1pdm09 strains (EC = 0.
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