Antiviral drug development by targeting RNA binding site, oligomerization and nuclear export of influenza nucleoprotein

The quasispecies of the influenza virus poses a significant challenge for developing effective therapies. Current antiviral drugs such as oseltamivir, zanamivir, peramivir and baloxavir marboxil along with seasonal vaccines have limitations due to viral variability caused by antigenic drift and shift as well as the development of drug resistance. Therefore, there is a clear need for novel antiviral agents targeting alternative mechanisms, either independently or in combination with existing modalities, to reduce the impact of influenza virus-related infections. The influenza nucleoprotein (NP) is a key component of the viral ribonucleoprotein complex. The multifaceted nature of the NP makes it an attractive target for antiviral intervention. Recent reports have identified inhibitors that specifically target this protein. Recognizing the importance of developing influenza treatments for potential pandemics, this review explores the structural and functional aspects of NP and highlights its potential as an emerging target for anti-influenza drugs. We discuss various strategies for targeting NP, including RNA binding, oligomerization, and nuclear export, and also consider the potential of NP-based vaccines. Overall, this review provides insights into recent developments and future perspectives on targeting influenza NP for antiviral therapies. © 2024