The recent re-emergence of Zika virus (ZIKV)1, a member of the Flaviviridae family, has become a global emergency. Currently, there are no effective methods of preventing or treating ZIKV infection, which causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women. However, the pathology induced by ZIKV is unique among flaviviruses, and knowledge of the biology of other family members cannot easily be extrapolated to ZIKV. Thus, structure-function studies of ZIKV proteins are urgently needed to facilitate the development of effective preventative and therapeutic agents. Like other flaviviruses, ZIKV expresses an NS2B-NS3 protease, which consists of the NS2B cofactor and the NS3 protease domain and is essential for cleavage of the ZIKV polyprotein precursor and generation of fully functional viral proteins. Here, we report the enzymatic characterization of ZIKV protease, and we identify structural scaffolds for allosteric small-molecule inhibitors of this protease. Molecular modeling of the protease-inhibitor complexes suggests that these compounds bind to the druggable cavity in the NS2B-NS3 protease interface and affect productive interactions of the protease domain with its cofactor. The most potent compound demonstrated efficient inhibition of ZIKV propagation in vitro in human fetal neural progenitor cells and in vivo in SJL mice. The inhibitory scaffolds could be further developed into valuable research reagents and, ultimately, provide a roadmap for the selection of efficient inhibitors of ZIKV infection.

Thermotolerance is a property of all organisms, but owing to their sessile nature, this trait is particularly important in plants. Basal thermotolerance is based on inherent tolerance to heat stress. Acquired thermotolerance is attained through stress-induced gene expression, often of those genes encoding heat shock proteins (HSPs). Both basal and acquired thermotolerance have been extensively studied in model species such as Arabidopsis thaliana (L.) Heynh., but much less is known about thermotolerance in wild plant species. The aims of this study were to examine the basal and acquired thermotolerance of four species of Boechera, and of A. thaliana. Mots-clés : Arabidopsis, Boechera, fluorescence de la chlorophylle, expression génique induite par la chaleur, stress thermique, thermotolérance.