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Towards a new generation of antiviruses

​A team from the CEA-IBITECS participated in the identification of a novel role for an enzyme, the protease MMP-12, in the immune response to viral infection. The researchers developed an inhibitor of MMP-12, which enhances the immune response in a rodent model. This work, published in Nature Medicine, opens the way for the development of new antiviral therapies.

Published on 29 April 2014

MMP-12, or “zinc macrophage metalloelastase”, is a protease1 produced by macrophages2 during inflammation. An international collaboration led by the University of British Columbia (Canada), with the participation of a team from the CEA-IBITECS, discovered a novel action of MMP-12 during viral infection. On the one hand, MMP-12 enters the nucleus of infected cells and triggers the secretion of interferon-alpha, a molecule known for its participation in the defense of the organism. On the other hand, outside of the cell, this same MMP-12 controls the desired level of interferon-alpha and degrades the excess that could be toxic! The intensity of the antiviral response is thereby limited.

Using an inhibitor of MMP-12 that they had previously developed, researchers from the CEA-IBITECS blocked this second action of MMP-12 in a rodent model, demonstrating in vivo that this enhances the therapeutic response to viral infection without toxicity. Additional observations of human cells infected by a virus appear to confirm this role in humans. The patented inhibitors of MMP-12 could therefore represent a new generation of antiviral treatments. Preclinical trials are already scheduled.

[1] An enzyme that hydrolyzes proteins
[2] White blood cell of the immune system

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