Modulation of virus-microtubule interaction as a tool for novel antiviral therapy.

Microtubules (MT) are essential cell filaments that function as roads are hollow cylinders. Nucleotide binding and the GTPase activity are the true fuel of this cellular machine, allowing their grow and shrinking. Remarkably, a wide-range of small molecules (known as microtubule-targeting agents, MTAs) contribute to the pharmacological modulation of tubulin, and some have been developed as drugs for the treatment of cancer, inflammatory diseases and as anti-helminthics.
MTs are key players during virus infection, being essential for the entry, egression and, trafficking to and from the virus replication site. The virus abuse of this host machinery is often mediated by motor proteins, or by MT plus-end tracking proteins. But increasing data are pointing toward direct protein-protein interaction between certain viral proteins and tubulin, which implies the modulation of these filaments by the virus on desire. However, there is a gap of knowledge between the origin (underlying mechanism of direct protein-protein interaction) and the consequence (cellular effect of hijacking the microtubular network by a viral protein) that is crucial to override for development of specific therapeutic strategies for viral infection diseases. We depart from the hypothesis that viral proteins exploit the MT network mimicking the regulatory Microtubule Associated proteins (MAPs) to control the intracellular transport and ensure the correct distribution of the viral factories within the host cell, to develop a new research line focused on understanding the regulation of MTs by viral proteins and how is this compared to known mechanisms driven by MAPs.
We plan to employ macromolecular crystallography (MX) and fiber diffraction (FD) at ALBA to unveil the mechanism involved MTs-viral structural proteins interaction and the effect on MTAs on it.