Respiratory syncytial virus phosphoprotein has NTPase and helicase-like activities

RNA helicases and helicase-like viral proteins are crucial for viral RNA replication and are prime targets for antiviral development. RSV infects nearly all children by age two, causing over 30 million acute lower respiratory infections, 3.6 million hospitalizations, and 100,000 deaths annually in children under five, while also posing a significant threat to immunocompromised adults and the elderly. In this study, we demonstrate for the first time that the RSV P has NTPase activity and unwinds RNA helices in an NTP-dependent manner. Mutagenesis and reverse genetics experiments confirm that these enzymatic activities are essential for RSV viability. These findings not only redefine RSV P as a multifunctional protein but also expand our understanding of the RSV replication machinery, highlighting the potential of targeting P for antiviral therapy.