RNA virus families have great genetic heterogeneity that allows wide tropism and cross-species transmission. This group evolved to maximize the manipulation of the cellular machinery for viral replication and the antagonism or evasion of conserved cellular pathways aiming to restrict viral infection. For successful replication, all RNA viruses must complete five stages.
First, key proteins in the viral envelope bind to target cell receptors and fuse with the host cell membrane (1-viral entry). Once in the cell cytosol, viral RNA is translated to make the viral proteins that are involved in the generation of the replication complex (2-RNA translation). Viral replication occurs inside cytoplasmic replication organelles or double membrane vesicles that protect the virus RNA from being detected (3-viral replication). Structural viral proteins are produced and package full-length genomes to complete virion formation (4-viral assembly). Viral particles undergo maturation through the ER-Golgi organelles, leading finally to viral egress from the cells (5-viral release). An exquisite balance between viruses and hosts must be achieved, where a virus must silence innate immune activation to complete its life cycle in the cell. A common strategy is to target essential steps of the viral lifecycle to inhibit viral replication, transmission and pathogenicity.
The Projects developed by the QCRG AViDD Program aim to disrupt key processes at different stages that can be used alone or in combinations to suppress viral infection and disease.
Lead: Shokat; Co-I: Doudna, Ruggero
Lead: Craik; Co-I: Arnold, Götte, Schulze-Gahmen, Hultquist, Shoichet
Lead: DeGrado; Co-I: Stroud, Hong
Lead: Fujimori; Co-I: Shokat, Vedadi, Shoichet
Lead: Fraser; Co-I: Shoichet, Ashworth