Innovative Compounds Enhance Cellular Defense Against Viruses
Researchers from the Massachusetts Institute of Technology (MIT) and partner institutions have unveiled a new class of antiviral compounds that empower host cells to combat a broad spectrum of viral infections. This breakthrough could pave the way for novel antiviral therapies targeting multiple viruses simultaneously.
The research team discovered these compounds while conducting an extensive screening of nearly 400,000 molecules, aiming to activate the integrated stress response pathway within human cells. This pathway serves as a defense mechanism against viral infections, becoming active in response to stressors such as viral presence.
In laboratory tests, these compounds demonstrated efficacy against various viruses, including respiratory syncytial virus (RSV), herpes virus, and Zika virus. Notably, they also showed promise in a mouse model, effectively reducing herpes virus infection.
As the research advances, the team intends to further evaluate these compounds against a wider array of viruses, with the ultimate goal of progressing to clinical trials. The researchers express enthusiasm for the potential of this work, emphasizing its significance in developing broad-spectrum antiviral agents.
The integrated stress response pathway is activated in human cells during viral infections due to the presence of double-stranded RNA, a byproduct of viral replication. By bolstering this pathway, the identified compounds could serve as promising candidates for antiviral drug development.
Traditionally, antiviral drugs are designed for specific viruses; however, this innovative approach seeks to modulate the host's cellular stress response, potentially leading to a new generation of antiviral treatments that are effective against various viral pathogens.
To facilitate the identification of these effective compounds, the researchers employed a novel optogenetic screening method. This bioengineering technique involves introducing light-sensitive proteins into cellular genomes, allowing precise control over the activation of the stress response pathway using light.
By applying blue light to human cells treated with the compounds, the researchers simulated viral infection, enabling them to measure survival rates and assess antiviral activity. From this screening process, approximately 3,500 compounds were identified as having potential antiviral properties, which were subsequently evaluated in detail.
Out of these, eight promising compounds were selected for further testing, leading to the identification of three top candidates designated as IBX-200, IBX-202, and IBX-204. In experiments with cells infected by Zika, herpes, and RSV, these compounds significantly diminished viral loads.
In animal studies, IBX-200 was tested on mice infected with herpes virus, resulting in a notable decrease in viral levels and improvement in symptoms. The compounds appear to activate enzymes involved in recognizing cellular stress, thus enhancing the stress response pathway and preparing cells to counteract viral threats.
The research team is committed to exploring additional compounds that can activate the integrated stress response, as well as investigating other cellular stress pathways that may have the potential to eliminate viral or bacterial infections.