# Antiviral Efficacy, Cytotoxicity, Transcriptomics, and Discriminatory Function of 3D8 scFv Against Dengue and Zika Viruses

## TL;DR

This study shows that the antibody fragment 3D8 scFv effectively inhibits dengue and Zika viruses with minimal side effects.

## Contribution

The study demonstrates 3D8 scFv's broad-spectrum antiviral activity and distinct host response signatures for dengue and Zika.

## Key findings

- 3D8 scFv reduces viral RNA, protein, and infectious particles in both dengue and Zika infections.
- Machine learning classifiers accurately distinguish ZIKV and DENV2 infections based on transcriptomic signatures.
- 3D8 scFv induces a limited protective stress response without significant cytotoxicity.

## Abstract

Flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) co-circulate widely and cause significant morbidity, yet effective broad-spectrum antivirals are limited. This study evaluated the antiviral efficacy, cytotoxicity, and host transcriptional responses to the nucleic acid–hydrolyzing antibody fragment 3D8 scFv in mono- and co-infection models. RNA sequencing of A549 cells treated with 3D8 scFv revealed a dose-dependent activation of the MAPK–HSP70 stress response, with minimal transcriptomic disruption at antiviral concentrations. Comparative transcriptomic analysis identified distinct host signatures for ZIKV and DENV2, and machine learning classifiers accurately distinguished infection states (AUC > 0.95). In Vero E6 cells, prophylactic treatment with 3D8 scFv significantly reduced viral RNA, protein expression, and infectious particle production for both viruses, including during co-infection. Optimized post-entry treatment also demonstrated antiviral activity. Cytotoxicity assays confirmed good tolerability at effective concentrations. These findings indicate that 3D8 scFv inhibits viral replication through early cleavage of viral nucleic acids while inducing a limited protective stress response, supporting its development as a broad-spectrum antiviral candidate.