Researchers at the Pacific Northwest National Laboratory (PNNL) have identified crucial cellular targets of the common cold virus, which could lead to a new strategy for defending against multiple viral infections. This breakthrough extends beyond the common cold, as the findings may also apply to other coronaviruses, such as those responsible for COVID-19 and Middle East Respiratory Syndrome (MERS).
The team aims to shift the focus from directly attacking specific viruses to enhancing the body’s defenses against various pathogens. According to biochemist John Melchior, one of the study’s authors, “A virus thrives by taking over the cellular machinery of its host, hijacking normal processes to churn out copies of itself.” The researchers believe that fortifying cellular structures susceptible to viral invasion can help prevent viruses from establishing infections.
This innovative approach may pave the way for developing a single drug capable of targeting multiple types of viruses. Co-author Amy Sims highlighted the advantages of this method: “When you target only the virus, it can produce strains that readily escape antiviral medications.” By focusing on the host cell’s functions essential for viral replication, the researchers hope to eliminate the pathways most viruses exploit to cause illness.
New Techniques Unveiled
The PNNL team employed a cutting-edge technique known as limited proteolysis-based mass spectrometry (LiP-MS) to analyze human cells infected by the common cold virus, HCoV-229E. This method allows scientists to identify not only the abundance of proteins in a sample but also any structural changes they undergo during infection. Understanding these changes is critical, as the shape of a protein determines its function and interactions with other molecules.
In their investigation, the researchers pinpointed eight viral targets, including two key molecular complexes involved in RNA processing. The virus utilizes these assemblies to take control of the host cell’s machinery for its own replication. One significant target identified is Nop-56, which normally verifies the legitimacy of RNA strands for protein production. When hijacked by the virus, Nop-56 disrupts the synthesis of human proteins, allowing rogue viral proteins to take over.
Another critical target is the spliceosome C-complex, which helps edit RNA strands. By commandeering this assembly, the virus diverts the cell’s energy from producing essential proteins to generating its own detrimental proteins.
Implications for Virus Defense
The researchers are optimistic that their findings will provide valuable insights into developing drugs that can combat a range of viral infections. Postdoctoral fellow Snigdha Sarkar, the study’s lead author, remarked, “Viruses can mutate quickly, and that poses a problem when targeting a virus directly. That obstacle is removed if you target proteins that many viruses rely upon in the host.”
Currently, the PNNL team is exploring existing antiviral compounds identified by scientists at Oregon Health & Science University. They are also leveraging artificial intelligence to rapidly identify new compounds that could interact with the identified molecular targets.
This research, published in the Journal of Proteome Research, represents a significant advancement in the quest to develop effective treatments against viral diseases. As the team continues its work, they hope that this foundational research will lead to novel therapeutic strategies that can protect against a variety of viral threats in the future.
