Abstract
The Zika virus (ZIKV) global epidemic prompted the World Health Organization to declare it a 2016 Public Health Emergency of International Concern. The overwhelming experience over the past several years teaches us that ZIKV and the associated neurological complications represent a long-term world-wide challenge to public health. Although the number of ZIKV cases in the Western Hemisphere has dropped since 2016, the need for basic research and anti-ZIKV drug development remains strong. Re-emerging viruses like ZIKV are an ever-present threat in the 21st century where fast transcontinental travel lends itself to viral epidemics. Here, we first present the origin story for ZIKV and review the rapid progress researchers have made toward understanding of the ZIKV pathology and in the design, re-purposing, and testing–particularly in vivo–drug candidates for ZIKV prophylaxis and therapy ZIKV. Quite remarkably, a short, but intensive, drug-repurposing effort has already resulted in several readily available FDA-approved drugs that are capable of effectively combating the virus in infected adult mouse models and, most importantly, in both preventing maternal-fetal transmission and severe microcephaly in newborns in pregnant mouse models.
Highlights
The overwhelming experience over the past several years teaches us that Zika virus (ZIKV) and the associated neurological complications represent a long-term world-wide challenge to public health
We first present the origin story for ZIKV and review the rapid progress researchers have made toward understanding of the ZIKV pathology and in the design, re-purposing, and testing– in vivo–drug candidates for ZIKV prophylaxis and therapy ZIKV
Asian ZIKV (Asian strain SZ01) infects neural progenitor cells (NPCs) in vivo and affects brain development resulting in cell-cycle arrest, cell apoptosis, differentiation inhibition, cortical thinning, and, microcephaly
Summary
Evidence for a ZIKV-induced dysregulation of neural development comes from the studies in which ZIKV was injected directly into the lateral ventricle of the fetal mouse brain. Asian ZIKV (Asian strain SZ01) infects neural progenitor cells (NPCs) in vivo and affects brain development resulting in cell-cycle arrest, cell apoptosis, differentiation inhibition, cortical thinning, and, microcephaly. Using cost-effective miniature spinning bioreactors, the authors demonstrated that ZIKV infection resulted in suppressed proliferation and increased cell death in the early stage cortical organoids Not surprisingly, these organoids exhibited certain macroscopic features resembling microcephaly (Xu et al, 2016a). A global proteome- and gene-expression wide view of ZIKV infection may provide the field with potential biomarkers and indicators of pathogenesis unseen with existing studies (Mao et al, 2016; Zhang et al, 2016a; Garcez et al, 2017) Applying this approach to vertical transmission may provide insights into the critical proteins in the brain involved in the development of microcephaly. The major goal of this work will be to identify biomarkers for ZIKVinduced microcephaly
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