Respiratory syncytial virus infection in macaques is not suppressed by intranasal sprays of pyrimidine biosynthesis inhibitors.

International audienceThere is imperious need for efficient therapies against ubiquitous and life-threatening respiratory viruses, foremost among them being the human respiratory syncytial virus (hRSV). Several research groups who performed functional screens for broad-spectrum antivirals identified compounds targeting the de novo pyrimidine biosynthesis pathway. Despite their strong antiviral activity in vitro, whether such antimetabolites are effective in vivo remains highly controversial. Here, we evaluated two potent pyrimidine biosynthesis inhibitors developed in our laboratory, IPPA17-A04 and GAC50, in a model of mild hRSV-infection in cynomolgus macaques. In this model, hRSV replication is restricted to the epithelium of the upper respiratory tract, and is compatible with a topical treatment by intranasal sprays. The local administration of palivizumab, a neutralizing anti-hRSV antibody used in clinics, significantly reduced virus replication. In contrast, pyrimidine biosynthesis inhibitors did not show any inhibitory effect on hRSV growth when delivered topically as experimented in our model. Our results should help to better define the potential applications of this class of antimetabolites in the treatment of viral infections

Infant feeding practices and sleep development in pre-schoolers from the EDEN mother- child cohort

International audienceSleep problems affect 20% to 30% of toddlers and preschoolers. Few longitudinal studies focused on the impact of infant feeding practices on sleep. We aimed to study the associations between feeding practices up to 8 months and trajectories of sleep quantity or quality from 2 to 5-6 years. Analyses included 1028 children from the EDEN mother-child cohort. Data were collected by self-administered questionnaires. Associations between feeding practices (breastfeeding, complementary feeding, use of thickened infant formula, night feeding) and sleep trajectories (sleep onset difficulties, night waking, nighttime in bed) were analyzed by multiple logistic regressions. Predominant breastfeeding for more than 4 months was associated with lower risk for belonging to the persistent sleep onset difficulties trajectory. Night feeding at 4 months or at 2 years of age was associated with higher risk for belonging to the persistent sleep onset difficulties trajectory and night feeding at 8 months was associated with higher risk for night waking and with higher risk for short nighttime in bed. Early introduction (<4 months) to complementary foods (excluding baby cereals) was related to lower risk for short nighttime in bed. Use of baby cereals or thickened infant formula was related neither to sleep quality nor to sleep quantity. In conclusion, infant feeding practices are associated with sleep trajectories in preschoolers, with notably a potential protective role of breastfeeding. Further researches are needed to clarify the mechanisms of these relationships