Joël Polidori

The development of innovative antiviral strategies is critical to address the global health threats posed by RNA viruses, including the Zika virus (ZIKV), which can cause severe neurological complications. The lipid transporter OxySterol Binding Protein (OSBP), essential for cholesterol and phosphatidylinositol 4-phosphate trafficking, is exploited by many positive-strand RNA viruses, making it an attractive novel antiviral target. This study investigates simplified analogues of macarangin B, a natural compound with potent OSBP-targeted antiviral activity against ZIKV, but limited stability due to its flavonol moiety. A series of analogues was synthesized, replacing the flavonol with a flavone core while retaining the essential hexahydroxanthene (HHX) motif. These compounds demonstrated improved stability, high OSBP binding affinity, and low cytotoxicity. The most active compounds exhibited antiviral activity comparable to established OSBP inhibitors and were stable in physiologic media, highlighting their potential as leads for therapeutic development. This work advances the structure-activity relationship (SAR) understanding of macarangin B analogues and provides a foundation for designing effective antivirals targeting in ZIKV infections.

The dagger nematode Xiphinema index has a major economic impact because of its transmission of Grapevine fanleaf virus to grapevines. This vector nematode, which was introduced into Western countries from the Middle East together with the domesticated grapevine, mostly reproduces by meiotic parthenogenesis, but microsatellite multilocus genotype (MLG) analysis has revealed the occurrence of rare sexual reproduction events in field conditions. In a previous 6-year study under controlled conditions, we evaluated the durability of resistance to X. index in accessions derived from a muscadine resistance source and reference accessions. In this previous study, we used an equal-proportion mixture of four lines (from Spain, Italy, Greece, and Iran) representative of X. index diversity as the inoculum, and we collected random samples in 3-, 4-, 5-, and 6-year-old vines. Here, we genotyped the individuals from these samples using the MLG technique, and we analyzed the changes in line frequency and the occurrence of sexual reproduction events between lines over time. The nematode lines differed in aggressiveness and hybrids between lines were detected at a low, but apparently increasing rate. Hybridization events were recovered in all accessions, regardless of resistance status and propagation type. Finally, our data provide the first evidence of sexual reproduction in the nematode X. index under controlled conditions.