SASAKI Y, Kakisaka M, Chutiwitoonchai N, Tajima S,. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity. Biochem Biophys Res Commun. 2014 May 22. pii: S000
Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC50 values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.
See Also:
Latest articles in those days:
- Generation of Nasal Cell-Derived Human Alveolar Organoids and Organoid-Macrophage Assembloids for in Vitro Lung Modeling 10 hours ago
- Determinants of the Seasonal Influenza Vaccination Uptake Among People Aged 50 Years or Above During and After the Pandemic: A Systematic Review 22 hours ago
- [preprint]A GIS-based framework for standardized environmental characterization in One-Health surveillance: a case study of HPAI monitoring in wetlands 22 hours ago
- First detection and transatlantic introduction of Influenza A(H3N2) subclade K (J.2.4.1) into Ecuador: insights from genomic sentinel surveillance 22 hours ago
- Assessment of influenza virus and coronavirus tropism, replication competence and disease severity in ex vivo and in vitro cultures of the human respiratory tract 2 days ago
[Go Top] [Close Window]


