Through screening by NMR spectroscopy, we discovered a novel scaffold (DPQ: 6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) that binds specifically to the influenza A virus RNA promoter. The solution structure of the RNA-DPQ complex reported here demonstrates that the internal loop is the binding site of DPQ. The scaffold exhibits antiviral activity against influenza viruses.
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http://dx.doi.org/10.1039/c3cc46973e | DOI Listing |
Emerg Microbes Infect
January 2025
Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People's Republic of China.
The H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified ten H9N2 strains exhibiting different lethality to chick embryos. Two representative strains, A/chicken/China/LN07/2016 (CKLN/07) and A/chicken/China/LN17/2016 (CKLN/17), with similar genomic background but different chick embryo lethality, were chosen to evaluate the molecular basis for this difference.
View Article and Find Full Text PDFMed Chem
January 2025
Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences of Agadir, Ibn Zohr University, Agadir, Morocco.
Background: We continue to struggle with the prevention and treatment of the influenza virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous fatalities. The threat of influenza remains a significant concern for global health, and the development of novel drugs targeting these viruses is highly desirable.
View Article and Find Full Text PDFiScience
January 2025
College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. China.
Pyroptosis plays an important role in attracting innate immune cells to eliminate infected niches. Our study focuses on how influenza A virus (IAV) infection triggers pyroptosis in respiratory epithelial cells. Here, we report that IAV infection induces pyroptosis in a human and murine airway epithelial cell line.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Departament de Nutrició, Ciències de l'Alimentació i Gastronomia, Facultat de Farmàcia i Ciències de l'Alimentació - Campus Torribera, Universitat de Barcelona, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain.
Assessing the binding mode of drug-like compounds is key in structure-based drug design. However, this may be challenged by factors such as the structural flexibility of the target protein. In this case, state-of-the-art computational methods can be valuable to explore the linkages between structural and pharmacological data.
View Article and Find Full Text PDFNat Commun
January 2025
National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China.
The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells.
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