In the project “Targeting the henipavirus polymerase complex: a structure and biochemistry directed approach” assays and reagents will be developed to assess biochemical activity and perform detailed structure-function analyses of henipavirus polymerases as it transitions through different conformations to perform viral mRNA transcription and genome replication. Using a systematic combination of biochemical assays, site-directed mutational analysis, cryo-EM maps, Fluorescence Resonance Energy Transfer, and Small-Angle X-ray Scattering analyses the research team will gather data to build high resolution models of the polymerase complex to understand how conformational states of the polymerase complex can affect biochemical activity. These data will be used to identify features of the polymerase that facilitate structural transitions and potential allosteric sites of inhibition. The 3-year project was initiated in October 2022 and is hosted by Boston University (BUMC), USA and the principal investigator is Professor Rachel Fearns.
The picture above is provided by Rachel Fearns and illustrates different stages of henipavirus transcription.