2025-11-17 パシフィック・ノースウェスト国立研究所(PNNL)
<関連情報>
- https://www.pnnl.gov/news-media/scientists-identify-two-key-targets-common-cold-virus
- https://pubs.acs.org/doi/10.1021/acs.jproteome.5c00400
ヒトコロナウイルス229Eは複製のために宿主細胞のRNAプロセシング複合体を乗っ取る Human Coronavirus-229E Hijacks Key Host-Cell RNA-Processing Complexes for Replication
Snigdha Sarkar,Song Feng,Hugh D. Mitchell,Madelyn R. Berger,Tong Zhang,Isaac K. Attah,Chelsea M. Hutchinson-Bunch,Victoria N. Prozapas,Kristin Engbrecht,Stephanie King,Amy C. Sims,and John T. Melchior
Journal of Proteome Research Published: September 12, 2025
DOI:https://doi.org/10.1021/acs.jproteome.5c00400
Abstract
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.
