Connessioni scientifiche n° 12: Luis Janiel Navarro Gonzalez

Characterization of the binding interface between Zika virus and human dynein for the development of potential antiviral drugs

Zika virus (ZIKV) has emerged as a major global health concern due to its rapid spread and
its association with severe neurological complications, including congenital microcephaly
and Guillain-Barré syndrome. Despite significant research efforts, no specific antiviral
treatments are currently available, highlighting the need to identify novel therapeutic targets.
In this context, the study of molecular interactions between viral and host proteins represents
a promising strategy to better understand viral replication and pathogenesis. ZIKV relies on
the host cytoskeleton to promote the intracellular trafficking of viral components toward
perinuclear replication sites. Recent findings from our group indicate a direct interaction
between the ZIKV envelope protein (pE) and the dimerization domain of human cytoplasmic
dynein 1 (NDD). This interaction has been supported by biochemical and cellular
approaches, as well as by biophysical measurements revealing binding in the micromolar
range. Based on this evidence, the proposed project aims to characterize the pE-NDD binding
interface through structural studies to elucidate the molecular determinants of this
association. Resolving this complex at atomic resolution will enable the identification of key
interfacial residues and provide mechanistic insights into how ZIKV may exploit dynein for
intracellular transport. Ultimately, this study will advance our understanding of virus-host
interactions and may support the rational design of antiviral strategies targeting the dynein-
virus interface.