bioRxivMicrobiologyPreprint
A novel viral protein translation mechanism reveals mitochondria as a target for antiviral drug development
Z. Cheng, D. Zhang, J. Chen, Y. Wu, X. Liu, L. Si, Z. Zhang, N. Zhang, Z. Zhang, W. Liu, H. Liu, L. Zhang, L. Song, L. S. C. Dunmall, J. Dong, N. R. Lemoine, Y. Wang
Abstract
The ongoing Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has acutely highlighted the need to identify new treatment strategies for viral infections. Here we present a pivotal molecular mechanism of viral protein translation that relies on the mitochondrial translation machinery. We found that rare codons such as Leu-TTA are highly enriched in many viruses, including SARS-CoV-2, and these codons are essential for the regulation of viral protein expression. SARS-CoV-2 controls the translation of its spike gene by hijacking host mitochondria through 5 leader and 3UTR sequences that contain mitochondrial localization signals and activate the EGR1 pathway. Mitochondrial-targeted drugs such as lonidamine and polydatin significantly repress rare codon-driven gene expression and viral replication. This study identifies an unreported viral protein translation mechanism and opens up a novel avenue for developing antiviral drugs. One Sentence SummaryMitochondria are a potential target for antiviral therapy
- organism: human
- assay: bulk RNA-seq
- research focus: drug response / drug discovery
- research focus: gene regulatory network inference
- approach: experimental assay
- approach: statistical model
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