CE44 - Biochimie et chimie du vivant

New strategies for decoding cyclophilin biological functions – CYP-TAC

Submission summary

Cyclophilins are a family of proteins that catalyzes the cis/trans isomerization of peptide bonds at proline residues, which facilitates protein folding. CypA, the most abundant cyclophilin isoform, has been described as a key player in viral infection for viruses such as HCV, dengue virus, coronaviruses and HIV-1. One hypothesis is that CypA plays a role in the virus-host interface, via the “cloaking” of viral RNA. Nevertheless, how these viruses exploit CypA to promote their replication remains poorly understood.
The Cyp-TAC project aims to decipher the role of CypA in viral infection for coronaviruses, by combining biochemical assays with two complementary chemical approaches: enzymatic inhibition and protein degradation with the PROTAC technology. To achieve this objective, the project regroups internationally recognized experts that have already worked together in the field of cyclophilins and coronavirus. The Cyp-TAC consortium has 3 objectives (1) generate a CypA specific inhibitor, starting from a Cyp inhibitor previously synthesized by the partners (2) design and synthesise a CypA-specific PROTAC molecule (3) study CypA-mediated coronaviruses RNA viral cloaking mechanism in an ex-vivo physiologically relevant 2D human primary nasal epithelium model.
The Cyp-TAC project will have an impact in the knowledge of virus-host interactions and could open the route for developing novel pan-viruses anti-viral agents.

Project coordination

Jean-François Guichou (Centre de Biologie Structurale)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

VHC Viruses-Hepatology-Cancers
CRCL Centre de Recherche en Cancérologie de Lyon
CBS Centre de Biologie Structurale

Help of the ANR 630,947 euros
Beginning and duration of the scientific project: October 2023 - 48 Months

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