Identification of Conserved Antiviral and Vaccine Targets Through Evolutionary and Structural Analysis of PB1 and PB2 Subunits of Influenza A Virus
The influenza genome is transcribed and replicated by an RNA polymerase complex. This complex consists of PB1 and PB2 subunits, playing a critical role in viral RNA synthesis and interaction with host cell proteins. The PB1 subunit forms the catalytic center of chain elongation, while the PB2 subunit recognizes the 5′ cap structures of host mRNAs, enabling their cleavage via PA and their use as primers for synthesis. Therefore, molecular-level analysis of the RNA polymerase complex is crucial for understanding the virus’s replication mechanism. The conserved structural regions of PB1 and PB2, along with their interactions with host proteins, make these subunits priority targets for both antiviral drug and vaccine development. Current studies indicate that PB1 and PB2 subunits contain binding sites that can be evaluated for vaccine and small molecule drug development. However, comprehensive bioinformatic analyses of the evolutionary conservation levels and selection pressures of target regions of PB1 and PB2 have not yet been conducted. This project aims to perform a long-term evolutionary mapping, which is lacking in the literature, by analyzing the variation dynamics, selection pressures, and structural conservation patterns of the PB1 and PB2 genes between 2009 and 2025.
This project is conducted by Helen Üce and Fatma Sevil Demirdağ, and supported by TUBİTAK 2209.