RICHLAND, Wash.—Scientists have made a breakthrough in understanding how the common cold virus infiltrates the human body, pinpointing crucial cellular checkpoints that serve as targets for the virus. This discovery, however, extends beyond just the common cold. Researchers are hopeful that their findings will pave the way for new strategies to protect against a variety of viruses, including those that cause severe illnesses like COVID-19.
The research team at the Department of Energy’s Pacific Northwest National Laboratory (PNNL) is shifting the paradigm of antiviral strategies. Instead of targeting specific viruses, they aim to bolster the body’s defenses against multiple viral threats simultaneously. This innovative approach could revolutionize how we combat viral pathogens.
Revolutionizing Antiviral Strategies
According to John Melchior, a biochemist and co-author of the study published in the Journal of Proteome Research, viruses thrive by hijacking the host’s cellular machinery. “We want to identify and then fortify the molecular complexes that are susceptible to many invading viruses—to stop viruses before they have a chance to take over the cell,” Melchior explained. By manipulating cellular control points, the team hopes to prevent viruses from replicating within host cells.
Virologist Amy Sims, co-corresponding author, highlighted the potential of this approach in combating various coronaviruses, from those causing mild symptoms to those leading to severe diseases like acute respiratory distress syndrome (ARDS). “This approach offers a pathway for using a single drug to stop multiple types of viruses,” Sims stated. By targeting host cell functions essential for viral replication, the researchers aim to eliminate common escape routes used by viruses.
Targeting Cellular Machinery
The PNNL team employed a cutting-edge technique known as limited proteolysis-based mass spectrometry (LiP-MS) to study human cells infected by HCoV-229E, a common cold virus. This technique allows scientists to observe changes in protein abundance and conformation, which are crucial for understanding protein function and interactions.
Among the identified targets were two molecular assemblies involved in RNA processing. One of these, Nop-56, is critical for validating RNA strands, allowing ribosomes to produce proteins. When the cold virus hijacks Nop-56, it disrupts normal protein production, favoring viral replication instead. Another target, the spliceosome C-complex, edits RNA strands. The virus’s control over this assembly further diverts the cell from its normal functions.
“We hope our work provides a list of common molecular targets that sets the foundation for the development of drugs that could block not just one but many viruses that cause disease,” said Snigdha Sarkar, a postdoctoral fellow and first author of the paper.
Future Directions and Broader Implications
Currently, the PNNL team is investigating existing compounds with antiviral potential, identified by scientists at Oregon Health & Science University. They are also leveraging artificial intelligence to rapidly pinpoint compounds that could influence the newly identified molecular targets.
This research is part of PNNL’s Predictive Phenomics Initiative, which seeks to understand how factors beyond genetic code influence the traits of living organisms. The initiative has significant implications for the bioeconomy and human health, particularly in predicting outcomes from environmental changes, such as viral infections.
As viruses continue to evolve, the need for broad-spectrum antiviral strategies becomes increasingly urgent. By focusing on common molecular targets within host cells, researchers hope to develop treatments that are resilient to viral mutations, offering a robust defense against both current and emerging viral threats.
The study’s authors, including Song Feng, Hugh Mitchell, Madelyn Berger, Tong Zhang, Isaac Attah, Chelsea Hutchinson-Bunch, Victoria Prozapas, Kristin Engbrecht, and Stephanie King, underscore the collaborative effort behind this pioneering research. The potential to transform antiviral treatment strategies marks a significant step forward in global health security.
