Characterisation of SARS CoV 2 membrane associated replication complexes – CoMemRep

Common to other positive stranded RNA viruses (+ssRNAv), such as dengue flavivirus or Chikungunya Alphavirus, SARS-CoV viral genome is synthesized, capped and polyadenylated by viral replication complexes, which are associated to intracellular membrane vesicles called viral factories. The aim of CoMemRep is to discover and provide high resolution structural information of large replication machinery of SARS-CoV-2 considering its membrane association. The project is reinforced by ground breaking results on a related virus: Chikungunya virus. The results will provide a large amount of new therapeutic targets for antivirals targeting membrane association and oligomerization of replication complexes, and will change our understanding of SARS replication and beyond, leading to an improvement of current inhibitors designed for isolated or small replication complex instead of complete assemblies of replication complexes. Thus, this project is aligned with the call aim of providing new therapeutic targets against Covid-19 pandemic.
The project will consist on the expression and structural characterization of membrane associated nonstructural proteins (nsps) of SARS-CoV-2 replication machinery (nsp3-4 and 6) for the subsequent assembly of the proteins involved in RNA synthesis and processing (nsp7-16).