Language

English

Publication Date

8-24-2025

Journal

bioRxiv

DOI

10.1101/2025.06.24.661395

PMID

40666986

PMCID

PMC12262275

PubMedCentral® Posted Date

8-24-2025

PubMedCentral® Full Text Version

Pre-Print

Abstract

Integrase-strand-transfer inhibitors have transformed HIV therapy, yet the widely prescribed drug dolutegravir (DTG) has been linked to developmental toxicity and its teratogenic mechanism remains uncertain. Here we use zebrafish to dissect DTG toxicity during early vertebrate development. DTG exposure from 2-4 h post-fertilization (hpf) to 24 hpf produced high mortality and abnormal morphology; co-treatment with folic acid or 5-methyltetrahydrofolate partially restored normal morphology, whereas calcium had no effect. Strikingly, supplementation with magnesium (Mg) rescued DTG-exposed embryos almost as effectively as folate, implicating magnesium availability in protection. In competitive binding assays, Mg increased binding of folate to purified folate receptor (FOLR1) by 30% in the presence of DTG. Maternal-zygotic zebrafish

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.