Identifikace sloučenin inhibujících vazbu čepičky na RNA polymerasu viru chřipky

Gregor, Jiří

The influenza A virus represents a significant global health threat due to its efficient transmission and the high variability of its genome, which underlies recurrent annual epidemics and, occasionally, pandemics. This disease has not only major clinical impact but also constitutes serious public health concerns. Although prophylactic vaccination is available, options for targeted antiviral therapy remain limited, underscoring the urgent need for novel and effective antiviral agents. VX-787 emerged as a promising candidate, functioning as a specific inhibitor of the five- prime cap-binding activity of the PB2 subunit of the influenza virus RNA-dependent RNA polymerase. This interaction is essential for the cap-snatching mechanism, a key step in viral genome transcription. Despite demonstrating the potent antiviral activity of VX-787, resistance- associated mutations in PB2 emerged during preclinical and clinical evaluation. Clinical trials were discontinued, as VX-787 did not demonstrate a definitive therapeutic advantage over the current standard of care. The aim of this work was to elucidate the molecular mechanisms of VX-787 resistance in selected PB2 mutants and to develop reliable screening methods for identifying new inhibitors of PB2 - five-prime cap interaction. Our results indicate that...

guest :: login Digital Repository
		Search		Submit		Help		About