TY - JOUR T1 - A novel viral protein translation mechanism reveals mitochondria as a target for antiviral drug development JF - bioRxiv DO - 10.1101/2020.10.19.344713 SP - 2020.10.19.344713 AU - Zhenguo Cheng AU - Danhua Zhang AU - Jingfei Chen AU - Yifan Wu AU - XiaoWen Liu AU - Lingling Si AU - Zhe Zhang AU - Na Zhang AU - Zhongxian Zhang AU - Wei Liu AU - Hong Liu AU - Lirong Zhang AU - Lijie Song AU - Louisa S Chard Dunmall AU - Jianzeng Dong AU - Nicholas R Lemoine AU - Yaohe Wang Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/19/2020.10.19.344713.abstract N2 - 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 3’UTR 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 Summary Mitochondria are a potential target for antiviral therapyCompeting Interest StatementThe authors have declared no competing interest. ER -