biostudies-literatureGiacchello IMinistero dell'Università e della Ricerca (MUR), Italy with PRIN 2022 PNRRMinistero dell'Università e della Ricerca (MUR), Italy with PRIN 2022EU fundingAssociazione Italiana per la Ricerca sul Cancro, AIRC, ItalyItalian Association for Cancer ResearchMinistero dell’Università e della Ricerca (MUR), ItalyNextGenerationEU-MUR PNRRFondazione Cassa di Risparmio di Padova e Rovigo, Italy954https://www.ebi.ac.uk/biostudies/studies/S-EPMC11279468biostudies-literatureUnknown16(7)The limited range of available flu treatments due to virus mutations and drug resistance have prompted the search for new therapies. RNA-dependent RNA polymerase (RdRp) is a heterotrimeric complex of three subunits, i.e., polymerase acidic protein (PA) and polymerase basic proteins 1 and 2 (PB1 and PB2). It is widely recognized as one of the most promising anti-flu targets because of its critical role in influenza infection and high amino acid conservation. In particular, the disruption of RdRp complex assembly through protein-protein interaction (PPI) inhibition has emerged as a valuable strategy for discovering a new therapy. Our group previously identified the 3-cyano-4,6-diphenyl-pyridine core as a privileged scaffold for developing PA-PB1 PPI inhibitors. Encouraged by these findings, PharmaceuticsExploring a New Generation of Pyrimidine and Pyridine Derivatives as Anti-Influenza Agents Targeting the Polymerase PA-PB1 Subunits Interaction.PMC11279468PE00000007P20222YKP855777 2020.016220223RYYFC25899Mori MMusumeci FSchenone SCarbone ACianciusi AFrancesconi VGiacchello IBertagnin CLoregian ABonomini AfalseExploring a New Generation of Pyrimidine and Pyridine Derivatives as Anti-Influenza Agents Targeting the Polymerase PA-PB1 Subunits Interaction.The limited range of available flu treatments due to virus mutations and drug resistance have prompted the search for new therapies. RNA-dependent RNA polymerase (RdRp) is a heterotrimeric complex of three subunits, i.e., polymerase acidic protein (PA) and polymerase basic proteins 1 and 2 (PB1 and PB2). It is widely recognized as one of the most promising anti-flu targets because of its critical role in influenza infection and high amino acid conservation. In particular, the disruption of RdRp complex assembly through protein-protein interaction (PPI) inhibition has emerged as a valuable strategy for discovering a new therapy. Our group previously identified the 3-cyano-4,6-diphenyl-pyridine core as a privileged scaffold for developing PA-PB1 PPI inhibitors. Encouraged by these findings, 2024-01-01T00:00:00Z2024 Jul2026-04-08T18:59:17.873Z2025-04-19T11:30:42.919ZS-EPMC112794683906565010.3390/pharmaceutics16070954