Key result
Mitochondrial-targeted drugs such as lonidamine and polydatin significantly repressed rare codon-driven gene expression and viral replication.
Why the study?
Do mitochondrial-targeted drugs like lonidamine and polydatin reduce viral replication in SARS-CoV-2 models?
Do mitochondrial-targeted drugs like lonidamine and polydatin reduce viral replication in SARS-CoV-2 models?
Mitochondria represent a novel target for antiviral drug development against SARS-CoV-2 by disrupting viral protein translation.
May suggest mitochondrial translation as antiviral target; leaves open clinical relevance in SARS-CoV-2.
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 therapy
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Cheng et al. (2020) studied SARS-CoV-2. Lonidamine and Polydatin vs. DMSO was evaluated on Viral replication and protein expression. Mitochondrial-targeted drugs such as lonidamine and polydatin significantly repressed rare codon-driven gene expression and viral replication.
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