Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics.

ABSTRACT: The adenosine analogue remdesivir has emerged as a front-line antiviral treatment for SARS-CoV-2, with preliminary evidence that it reduces the duration and severity of illness¹.Prior clinical studies have identified adverse events^1,2, and remdesivir has been shown to inhibit mitochondrial RNA polymerase in biochemical experiments⁷, yet little is known about the specific genetic pathways involved in cellular remdesivir metabolism and cytotoxicity. Through genome-wide CRISPR-Cas9 screening and RNA sequencing, we show that remdesivir treatment leads to a repression of mitochondrial respiratory activity, and we identify five genes whose loss significantly reduces remdesivir cytotoxicity. In particular, we show that loss of the mitochondrial nucleoside transpor

SUBMITTER: Akinci E 

PROVIDER: S-EPMC7457617 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature