# Immunostimulatory nucleic acid nanoparticles establish antiviral state to inhibit viral infection and replication

## TL;DR

This paper shows that immunostimulatory nanoparticles can create an antiviral state in cells, blocking multiple viruses from infecting and replicating.

## Contribution

The study introduces iNANPs as a novel broad-spectrum antiviral platform effective against diverse viruses.

## Key findings

- iNANPs induce strong interferon responses that restrict viral infection.
- The antiviral effect was observed against multiple viruses including VSV, SeV, and RSV.
- iNANPs establish a protective state that impairs replication of all tested viruses.

## Abstract

Establishing a rapid, broad-spectrum antiviral state in human cells offers a promising strategy to combat viral infections, especially when vaccines or pathogen-specific treatments are unavailable. Here, we evaluate immunostimulatory nucleic acid nanoparticles (iNANPs), identified as potent innate immune activators, for their ability to induce protective antiviral states. By mimicking pathogen-associated molecular patterns, iNANPs engage intracellular pattern recognition receptors to stimulate type I and III interferon responses. We tested iNANPs for antiviral efficacy against a replication-incompetent lentiviral vector pseudotyped with vesicular stomatitis virus (VSV) G protein, as well as replication-competent viruses, including VSV, Sendai virus (SeV), and respiratory syncytial virus (RSV). These viruses vary in their mechanisms of innate immune activation and evasion, providing a robust system to assess iNANP activity. Our results demonstrate that iNANPs dramatically restrict viral infection via induction of a robust IFN response, establishing an antiviral state that impairs replication of all tested viruses. This study highlights the potential of iNANPs as a broad-spectrum antiviral prophylactic platform.