- Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases. (2016) Reguera J, Gerlach P, Cusack S. Curr Opin Struct Biol 36 75-84 PMID:26826467
- Comparative Structural and Functional Analysis of Bunyavirus and Arenavirus Cap-Snatching Endonucleases. (2016) Reguera J, Gerlach P, Rosenthal M, Gaudon S, Coscia F, Gunther S, Cusack S. PLoS Pathog 12 e1005636 PMID:27304209
- Atomic Structure and Biochemical Characterization of an RNA Endonuclease in the N Terminus of Andes Virus L Protein. (2016) Fernandez-Garcia Y, Reguera J, Busch C, Witte G, Sanchez-Ramos O, Betzel C, Cusack S, Gunther S, Reindl S. PLoS Pathog 12 e1005635 PMID:27300328
- Structural Insights into Bunyavirus Replication and Its Regulation by the vRNA Promoter. (2015) Gerlach P, Malet H, Cusack S, Reguera J. Cell 161 1267-79 PMID:26004069
Our team focuses on understanding viral infection mechanisms often ruled by the interplay of viral proteins, cellular proteins and nucleic acids assembled into multifunctional complexes. The aim is to understand the mechanisms by which the multiple enzymatic activities are coordinated between them and regulated to efficiently carry out infection. To reach our goals we use a broad range of biochemical and biophysical technics combined with X-ray crystallography and electron microscopy.
The mainstream of our research is the functional and structural characterization of the alphavirus replication complex. Alphavirus, like chikungunya virus (CHIK) or eastern equine encephalitis virus (EEEV), cause zoonotic infectious diseases with high impact in global human health. The viral genome replication and gene expression is carried out by the multifunctional viral replication complex. Interestingly this complex can adopt different functions depending on its state of maturation. Our goal is to structurally and functionally characterize the different functional states of the replication complex in order to propose an integrative mechanistic model accurately describing at the molecular level the viral infection cycle and its regulation. The results will provide invaluable insights and tools for the development of new strategies for the treatment of these concerning infectious diseases.