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Development of therapeutic compounds based on the molecular interaction sites between the A238L viral protein and the transcriptional complexes that regulate the synthesis of pro-inflammatory and tumor mediators

18th national competition for scientific and technical research

Interactome: pathological implications

Senior Researcher : Yolanda Revilla Novella

Research Centre or Institution : Centro de Biología Molecular "Severo Ochoa". CSIC-Universidad Autónoma de Madrid


In the past, most drugs were identifying the active principle of traditional remedies or by random discovery. A new approach is to know the molecular basis of the disease, discovering a gene, a molecular mechanism or an "interactoma", related to the origin of the disease. This allows to identify specific targets, from which, using the virtual screening of chemyothecas, select a hit that constitutes the starting point until obtaining a series of candidates on which to work in the preclinical phases.

One of the objectives in this project has been to evaluate the role of a therapeutic target in inflammation and cancer of the A238L interaction site, mimicking the molecular mechanism of the viral protein, which we have shown to behave as a general inhibitor of transactivation inducible and has already given way to a functional hit in the mouse.
Using a similar strategy and since A238L interacts with transcription factors involved in inducible transcription modulating proinflammatory mediators, (including type I IFN, a potent antiviral), we intend to find possible therapeutic molecular targets mimicking new functional interaction sites of this protein. It is noteworthy that during this project we have found the role of A238L as a potent inhibitor of type I IFN, through its interaction with the IKK€ kinase, which open an interesting opportunity for SARS-2 application.
We believe that this strategy will enable, through the use of virtual screening techniques, followed by techniques of medical chemistry and experiments in cellular and mouse models, the discovery of new anti-inflammatory, antiviral (including SARS-2 inhibitors ) and anti tumor compounds.


Scientific Production
Magazine Articles 1
Communications at national conferences 1
Communications at international conferences 1


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