Preventive effects of folic acid on Zika virus-associated poor pregnancy outcomes in immunocompromised mice.

Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.

Infants with microcephaly due to ZIKA virus exposure: nutritional status and food practices.

BACKGROUND: Children with microcephaly due to vertical exposure to Zika virus are an interesting population for investigation. Highlighted among their unique aspects are those related to nutrition due to its impact on child growth and development. Knowledge about the nutrition of microcephalic infants can help mothers and caregivers provide better care. Thus, this study aimed to describe the nutritional status and feeding practices of infants with microcephaly due to Zika virus exposure at birth and 12-23 months of age. METHODS: This is a descriptive study developed from a cohort of patients attending a public institution of reference. A total of 65 infants attended outpatient nutrition clinics. The food practices were described using the 24-h food recall and food consumption indicators. Anthropometric measurements and consultations were made using the Child Health Handbook to obtain information on the nutritional status (weight, height and head circumference) at the time of consultation and birth. RESULTS: There was a significant decrease in z-scores for weight, height and head circumference (HC) from birth to the time of the consultation. However, most infants did not show weight-for-height deficits. Additionally, HC was correlated with the anthropometric indices weight-for-age, height-for-age, body mass index-for-age and weight-for-height. CONCLUSION: Infants exhibited a worsening of their nutritional status between birth and the time of their consultation, notably when we evaluated the indices of height and head circumference for age. The main inadequacies regarding dietary practices were low food diversity, use of ultra-processed products and low lipid intake.

Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.

Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public.