ArticleProceedings of the National Academy of Sciences of the United States of America2016
Zika virus cell tropism in the developing human brain and inhibition by azithromycin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04349592 (Randomized Placebo-controlled Trial of Hydroxychloroquine With or Without Azithromycin for Virologic Cure of COVID-19), which is not on this map. Cited by 298 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized Placebo-controlled Trial of Hydroxychloroquine With or Without Azithromycin for Virologic Cure of COVID-19
Who cites it
298 citing papers in PubMed, 5 syntheses or guidelines pooled it, 509 citations in OpenAlex.
- Pooled it
- The Spectrum of Antibiotic Prescribing During COVID-19 Pandemic: A Systematic Literature Review.Microbial drug resistance (Larchmont, N.Y.) · 2021Pooled it
- Use of hydroxychloroquine and chloroquine in patients with COVID-19: a meta-analysis of randomized clinical trials.Pathogens and global health · 2021Pooled it
- The Multifaceted Roles of TAM Receptors during Viral Infection.Virologica Sinica · 2021Pooled it
- Meta-analysis of honey bee neurogenomic response links Deformed wing virus type A to precocious behavioral maturation.Scientific reports · 2020Pooled it
- Reduction of Coronavirus Burden With Mass Azithromycin Distribution.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Trial
- RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.International journal of antimicrobial agents · 2020Trial
- Association of the eukaryotic vaginal virome with prophylactic antibiotic exposure and reproductive outcomes in a subfertile population undergoing in vitro fertilisation: a prospective exploratory study.BJOG : an international journal of obstetrics and gynaecology · 2020Trial
- Review
- Polyamines as Gatekeepers of Virus Replication and Central Nervous System Homeostasis.Pathogens (Basel, Switzerland) · 2026Review
- Breaking barriers and beyond: Mechanisms and pathological implications of Zika virus traversal across blood-tissue interfaces.Virologica Sinica · 2026Review
- Arboviruses in Cancer therapy: pros and cons.Journal of neurovirology · 2026Review
- Old drugs, new weapons: current trends in repurposing therapies against antimicrobial resistance.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- Comparison of human cerebral organoids infected with wild-type Zika versus attenuated DN-2 virus strains uncovers differences in host immune responses.Cell communication and signaling : CCS · 2025Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Emerging brain organoids: 3D models to decipher, identify and revolutionize brain.Bioactive materials · 2025Review
- Challenges and Opportunities for Post-COVID Pulmonary Disease: A Focused Review of Immunomodulation.International journal of molecular sciences · 2025Review
- Multi-omics analysis reveals key immunogenic signatures induced by oncolytic Zika virus infection of paediatric brain tumour cells.Scientific reports · 2025Article
- Ex vivo study of neuroinvasive and neurotropic viruses: what is current and what is next.FEMS microbiology reviews · 2025Review
- Electro-polymerization of modified carbon paste sensor for detecting azithromycin.Scientific reports · 2025Article
238 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation. In the brain, ZIKV preferentially infected neural stem cells, astrocytes, oligodendrocyte precursor cells, and microglia, whereas neurons were less susceptible to infection. These findings suggest mechanisms for microcephaly and other pathologic features of infants with congenital ZIKV infection that are not explained by neural stem cell infection alone, such as calcifications in the cortical plate. Furthermore, we find that blocking the glia-enriched putative viral entry receptor AXL reduced ZIKV infection of astrocytes in vitro, and genetic knockdown of AXL in a glial cell line nearly abolished infection. Finally, we evaluate 2,177 compounds, focusing on drugs safe in pregnancy. We show that the macrolide antibiotic azithromycin reduced viral proliferation and virus-induced cytopathic effects in glial cell lines and human astrocytes. Our characterization of infection in the developing human brain clarifies the pathogenesis of congenital ZIKV infection and provides the basis for investigating possible therapeutic strategies to safely alleviate or prevent the most severe consequences of the epidemic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.