| Accession | PRJCA047637 | ||||||||||||||||||||||||
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| Title | Transcriptomics-Driven Antiviral Drug Screening Identifies ATF6 as a Homeostatic Regulator of ER stress and Innate Immunity | ||||||||||||||||||||||||
| Relevance | Medical | ||||||||||||||||||||||||
| Data types | Raw sequence reads | ||||||||||||||||||||||||
| Organisms | Severe acute respiratory syndrome coronavirus 2 | ||||||||||||||||||||||||
| Description | SARS-CoV-2 caused a global pandemic with widespread devastation on health system and many other aspects. To establish an effective treatment screening system, we used deep RNA sequencing techniques to study gene expression changes of host cells (Huh7 and Vero-E6) along with viral replication dynamics upon SARS-CoV-2 infection. The imbalanced host genes serve as the SARS-CoV-2 expression signatures for computational screening of the compounds with anti-viral potential, following the concept of Connectivity Map (cMap). This study found that acute activation of host innate immunity pathway plays an essential role to suppress SARS-CoV-2 replication, and a variety of compounds with pharmacological activity against SARS-CoV-2 were successfully identified. Further transcriptomic comparison revealed the endoplasmic reticulum (ER) stress as the key machinery underneath the efficacy difference. Mechanistically, ATF6, an ER stress regulator, promotes viral replication by tempering PERK/IRE1-driven rapid activation of NF-κB and innate immunity (e.g., IL-1α, TNF-α). This work positions ER stress modulation, particularly ATF6 targeting, as a strategy to balance antiviral defense and inflammatory toxicity, offering a roadmap for pan-coronavirus therapeutics. With these results, we established a paradigm for transcriptomic signature-based drug screening system for future treatment development of virus pandemics. | ||||||||||||||||||||||||
| Sample scope | Multispecies | ||||||||||||||||||||||||
| Release date | 2025-10-23 | ||||||||||||||||||||||||
| Grants |
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| Submitter | Yan Zhao (yanzhao1006@gmail.com) | ||||||||||||||||||||||||
| Organization | Southern University of Science and Technology | ||||||||||||||||||||||||
| Submission date | 2025-10-09 |