MERS-CoV

Research Pinpoints Key Cellular Targets for Broad-Spectrum Antiviral Development

Scientists at the Pacific Northwest National Laboratory (PNNL) have identified eight targets within human cells exploited by viruses, with a particular focus on two molecular assemblies crucial for RNA processing. This research, published in the Journal of Proteome Research, offers a potential pathway for developing antiviral drugs effective against a range of viruses, including the common cold.

The team discovered that the virus commandeers these cellular mechanisms, diverting them from their normal function to replicate itself. Blocking the virus’s interaction with these assemblies significantly reduced its ability to reproduce within human lung cells.

specifically,the research highlighted Nop-56 and the spliceosome C-complex as key targets. Nop-56 normally adds a chemical marker to RNA, signaling its legitimacy for protein production by ribosomes. The virus hijacks this process, leading to the destruction of human RNA and the approval of viral proteins instead. Similarly, the spliceosome C-complex, responsible for editing RNA by removing non-essential regions, is exploited by the virus to prioritize the creation of its own proteins over those needed by the host.

“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,” explained Snigdha Sarkar, a postdoctoral fellow and the paper’s first author.

The researchers emphasize the advantage of targeting host cell proteins rather than the virus itself. “Viruses can mutate quickly, and that poses a problem when targeting a virus directly,” Sarkar added. “That obstacle is removed if you target proteins that many viruses rely upon in the host.”

Currently, the PNNL team is investigating existing compounds identified by scientists at Oregon Health & Science University for their antiviral potential. They are also utilizing artificial intelligence to accelerate the discovery of new compounds that could disrupt the identified molecular targets.

This work is supported by PNNL’s Predictive Phenomics Initiative, which aims to understand how factors beyond genetics influence traits in living organisms. The initiative seeks to predict outcomes from changes within the body, such as those triggered by viral infections, with implications for bioeconomy and human health.

The research team includes Melchior, Sarkar, Sims, Song feng, Hugh Mitchell, Madelyn Berger, Tong Zhang, Isaac Attah, Chelsea Hutchinson-Bunch, Victoria Prozapas, Kristin Engbrecht, and Stephanie King. The study is documented in Sarkar, S.,et al. (2025). Human Coronavirus-229E hijacks Key Host-Cell RNA-Processing Complexes for Replication. Journal of Proteome Research. doi: 10.1021/acs.jproteome.5c00400.