MIT Researchers Uncover Potential Antiviral Drugs Targeting Stress Response

In a groundbreaking study published on July 14, 2025, in the journal *Cell*, researchers from the Massachusetts Institute of Technology (MIT) have identified promising compounds that enhance the integrated stress response (ISR) in human cells, potentially paving the way for broad-spectrum antiviral therapies against a variety of viruses, including Zika, herpes, and respiratory syncytial virus (RSV). This research marks a significant advancement in the field of antiviral drug discovery, utilizing a unique optogenetic platform for high-throughput screening of over 370,000 compounds.

The study, led by Felix Wong, former MIT postdoctoral researcher and current CEO of Integrated Biosciences, emphasizes the innovative approach of harnessing the ISR pathway, which is activated when cells face viral infections or other stressors. The ISR pathway, when triggered, halts viral protein synthesis, effectively stunting viral replication. “We hypothesize that modulating the host cell stress response could lead to a new class of broad-spectrum antivirals,” Wong stated in a news release.

This research builds upon previous findings that indicate the ISR pathway’s role in combatting viral infections. According to Dr. James Collins, a professor of medical engineering and science at MIT, the successful identification of compounds that activate this pathway could revolutionize how antiviral drugs are developed. “Our work allows us to harness the stress response of host cells to identify and develop broad-spectrum antivirals,” Collins noted.

Through their novel optogenetic platform, the researchers were able to simulate viral infections in human cells and observe how different compounds influenced the ISR. Their screening process led to the identification of nearly 3,500 compounds exhibiting antiviral activity. Of these, three compounds—IBX-200, IBX-202, and IBX-204—showed remarkable efficacy, notably reducing viral loads in cells infected with Zika and herpes viruses while sparing uninfected cells from cytotoxic effects.

The implications of this research extend beyond immediate antiviral applications. As the world continues to face emerging viral threats, the ability to create effective treatments that activate the body’s innate defenses represents a significant leap in medical science. This study lays the groundwork for further evaluations and potential clinical trials of the compounds against additional viral pathogens. Dr. Collins emphasized the importance of this research in a broader context, stating, “If the ISR is fully activated in response to a viral infection, our compounds can maximize the antiviral response, providing a robust defense even against low levels of virus.”

As the researchers prepare for further studies to assess the compounds against more viruses, the scientific community remains optimistic about the potential of ISR-targeting therapies. This breakthrough not only highlights the innovative approaches being undertaken in viral research but also underscores the importance of interdisciplinary collaboration in addressing global health challenges.