# Host‐Directed Antiviral Activity of SB2960 Through Selective Induction and Remodeling of Stress Granules

## TL;DR

SB2960 is a small molecule that boosts the body's antiviral defenses by forming stress granules, offering a new approach to treat various viral infections.

## Contribution

SB2960 is a novel small molecule that induces stress granules and shows broad-spectrum antiviral activity by targeting RACK1.

## Key findings

- SB2960 suppresses viral replication with minimal cytotoxicity by modulating host immune responses.
- SB2960 engages RACK1, a key regulator of stress granule dynamics.
- SB2960 alters stress granule composition and modulates antiviral gene expression.

## Abstract

The increasing prevalence of emerging infectious diseases highlights the urgent need for broad‐spectrum antiviral therapeutics. Here, the discovery of SB2960, a small molecule, is reported that promotes stress granule (SG) formation and exhibits potent antiviral activity across diverse viral species. SB2960 suppresses viral replication with minimal cytotoxicity by modulating host antiviral immune responses. Target identification studies reveal that SB2960 engages receptor for activated protein C kinase 1 (RACK1), a key regulator of SG dynamics. Integrated transcriptomic and proteomic analyses further demonstrate that SB2960 alters the composition of SG and modulates the expression of antiviral genes. These findings establish SB2960 as a promising host‐directed broad‐spectrum antiviral agent and a valuable probe for investigating SG biology in the context of viral infection.

Amid the ongoing threat of emerging viral pathogens, host‐directed antivirals offer a strategy to overcome viral mutation and drug resistance. SB2960, a small‐molecule inducer of stress granules (SGs), exhibits potent broad‐spectrum antiviral activity with minimal cytotoxicity. By selectively remodeling SG composition and engaging receptor for activated protein C kinase 1 (RACK1), SB2960 provides a chemical tool to dissect SG biology and a promising lead for antiviral therapeutics.