Human Coronavirus-229E Hijacks Key Host-Cell RNA-Processing Complexes for Replication

作者：Snigdha Sarkar, Song Feng, Hugh Mitchell, Madelyn Berger, Tong Zhang, Isaac Attah, Chelsea Hutchinson-Bunch, Victoria Prozapas, Kristin Engbrecht, Stephanie King, Amy Sims, John Melchior · 发表于：Journal of Proteome Research · 年份：2025 · DOI：10.1021/acs.jproteome.5c00400 · 被引用次数：5 · 研究领域：SARS-CoV-2 and COVID-19 Research、Viral gastroenteritis research and epidemiology、Viral Infections and Immunology Research

The recent rise in zoonotic coronavirus outbreaks underscores the urgency to understand virus-host interactions to develop potent antiviral therapeutics. Systems biology approaches, particularly proteomics, have been invaluable in providing a global overview of such interactions. However, these conventional approaches rely on measuring protein abundance changes that do not capture all molecular changes associated with altered regulatory pathways. In this study, we employed a high-throughput structural proteomics approach called limited proteolysis-based mass spectrometry (LiP-MS) to capture protein conformational changes, which we demonstrate are better proxies for functional alterations. We applied this tool to profile the molecular landscape of different human lung cells following human coronavirus-229E (HCoV-229E) infection. We found that HCoV-229E uses a multipronged approach to hijack key RNA-processing pathways and assemblies as part of a host-shutoff strategy to achieve effective replication. We confirm our results with structural data derived from changes in the assemblies after infection. We go on to show that modulation of two of these assemblies, the Nop56-associated pre-rRNA complex and the spliceosome C-complex, can attenuate HCoV-229E replication, indicating that we have identified viable host-cell therapeutic targets with potential to provide broad efficacy against coronavirus infection.