PIF2024 - DESVELANDO LAS BASES MOLECULARES DE LA REPLICACION DE VIRUS RNA - PID2023-148560NB-I00

Emerging, zoonotic viral infectious diseases pose a now widely recognized, serious health risk to humans. Most of these diseases are caused by RNA viruses and have a reservoir in the animal population. One way to limit the impact of RNA viruses is to prevent their replication and an extensive knowledge of the replication mechanisms used by these pathogens is therefore essential. In this project, we will fully characterize the structure and function of different multicomponent complexes involved in replication of two important pathogens: Menglà virus (MLAV), a recently discovered filovirus, considered a new potential human pathogen, and the Coronavirus SARS-CoV-2. These complexes will be studied in the context of different functional states and, in the case of SARS-CoV-2, mimicking different virus variants. The expected results will provide fundamental knowledge on the functioning of theses replication machineries that may be critical for the development of new therapeutic strategies. The multidisciplinary nature of this project that combines different structural methods, X-ray, Cryo-EM, SAXS, with multiple biochemical and biophysical techniques to understand the composition, structure and dynamics of viral replication complexes, along with in vitro and in cell activity assays, will offer an ideal context to train a new generation of scientists motivated to understand the molecular bases of infectious diseases.