doi.org/10.1016/j.cell.2025.06.024
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Scientists at MIT and other institutions have discovered compounds that help human cells defend themselves against viral infections by activating a natural protective mechanism called the integrated stress response pathway
These compounds could become antiviral drugs capable of fighting not just one, but several types of viruses, such as Zika, herpes, and respiratory syncytial virus (RSV).
The researchers tested nearly 400,000 molecules and identified those that activate this defense pathway in cells.
In experiments with human cells, the compounds were able to protect against RSV, herpes, and Zika infections.
One of the compounds was also tested in mice infected with herpes, showing positive results.
“We are very excited about this work, which uses the cellular stress response to find and develop broad-spectrum antivirals,” said MIT professor James Collins.
He and Maxwell Wilson of the University of California, Berkeley, are the lead authors of the study, published in the journal *Cell*.
Felix Wong, a former MIT researcher and leader of the company Integrated Biosciences, is the lead author of the paper.
The research also involved scientists from other institutions, such as Illumina Ventures and Princeton University.
Strengthening Cell Defense
In human cells, the integrated stress response pathway is activated when there is a viral infection or other stresses, such as nutrient deprivation.
During an infection, the presence of double-stranded RNA, produced by viruses, causes the cell to stop producing proteins, hindering the virus’s multiplication.
Scientists believe that compounds that strengthen this pathway could be used as new antivirals effective against various viruses.
“Typically, antivirals are designed to combat a specific virus,” explains Wong.
“We think that activating the cellular stress response could create a new class of antivirals that affect something essential for the multiplication of all viruses.”
To find these compounds, the researchers used a technique called optogenetics, which allows cellular processes to be controlled with light.
They modified a protein called PKR, which activates the stress pathway, so that it could be activated by blue light, simulating a viral infection.
They then tested the 400,000 molecules on human cells exposed to light, determining which compounds increased cellular defense.
The analysis revealed approximately 3,500 molecules with antiviral potential, which were further studied.
Fighting Infections
The researchers chose eight promising compounds and tested their ability to fight viruses without harming human cells.
Of these, three stood out: IBX-200, IBX-202, and IBX-204. In cells infected with Zika, herpes, or RSV, these compounds significantly reduced the amount of virus.
In mice with herpes, the compound IBX-200 reduced the viral load and improved symptoms.
Experiments showed that these compounds activate an enzyme that detects stress, preparing cells to better respond to viral infections.
When applied to uninfected cells, the compounds have no effect.
The scientists now plan to test these compounds against other viruses and search for new molecules that activate the stress response pathway or other cellular defenses against viral or bacterial infections.
The research was funded by the Defense Threat Reduction Agency, the National Science Foundation, the U.S. Army Research Office, and Integrated Biosciences.
Published in 07/22/2025 06h32
Text adapted by AI (Grok) and translated via Google API in the English version. Images from public image libraries or credits in the caption. Information about DOI, author and institution can be found in the body of the article.
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