The evaluation of DNA-linked inhibitor antibody and AlphaScreen assays for high-throughput screening of compounds targeting the cap-binding domain in influenza a polymerase.

The PB2 subunit of the influenza virus polymerase complex is essential for viral replication, primarily through a mechanism known as cap-snatching. In this process, PB2 binds to the 5' cap structure of host pre-mRNAs, enabling the viral polymerase to hijack the host transcriptional machinery. This binding facilitates the cleavage and integration of the capped RNA fragment into viral mRNA, thereby promoting efficient viral replication.

Structural basis of the histone ubiquitination read-write mechanism of RYBP-PRC1.

Histone H2A monoubiquitination (H2Aub1) by the PRC1 subunit RING1B entails a positive feedback loop, mediated by the RING1B-interacting protein RYBP. We uncover that human RYBP-PRC1 binds unmodified nucleosomes via RING1B but H2Aub1-modified nucleosomes via RYBP. RYBP interactions with both ubiquitin and the nucleosome acidic patch create the high binding affinity that favors RYBP- over RING1B-directed PRC1 binding to H2Aub1-modified nucleosomes; this enables RING1B to monoubiquitinate H2A in neighboring unmodified nucleosomes.

Kinetic, Thermodynamic, and Structural Analysis of Drug Resistance Mutations in Neuraminidase from the 2009 Pandemic Influenza Virus.

Neuraminidase is the main target for current influenza drugs. Reduced susceptibility to oseltamivir, the most widely prescribed neuraminidase inhibitor, has been repeatedly reported. The resistance substitutions I223V and S247N, alone or in combination with the major oseltamivir-resistance mutation H275Y, have been observed in 2009 pandemic H1N1 viruses.