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10.1101/2020.08.27.270819 http://scihub22266oqcxt.onion/10.1101/2020.08.27.270819 32869031!7457617!32869031     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       bioRxiv 2020 ; ä (ä): ä Nephropedia Template TP {{tp|p=32869031|t=2020. Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics |pdf=|usr=}}{{32869031}} gab.com Text Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics JO: bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=32869031 #FOAvip 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 illness(1).Prior clinical studies have identified adverse events(1,2), and remdesivir has been shown to inhibit mitochondrial RNA polymerase in biochemical experiments(7), 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 transporter SLC29A3 mitigates remdesivir toxicity without a commensurate decrease in SARS-CoV-2 antiviral potency and that the mitochondrial adenylate kinase AK2 is a remdesivir kinase required for remdesivir efficacy and toxicity. This work elucidates the cellular mechanisms of remdesivir metabolism and provides a candidate gene target to reduce remdesivir cytotoxicity. Twit Text FOAVip Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics ????bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=32869031 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32869031 #FOAvip English Wikipedia <ref>{{Cite pmid|32869031}}</ref> Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics #MMPMID32869031 Akinci E; Cha M; Lin L; Yeo G; Hamilton MC; Donahue CJ; Bermudez-Cabrera HC; Zanetti LC; Chen M; Barkal SA; Khowpinitchai B; Chu N; Velimirovic M; Jodhani R; Fife JD; Sovrovic M; Cole PA; Davey RA; Cassa CA; Sherwood RI bioRxiv 2020[Aug]; ä (ä): ä PMID32869031show ga 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 illness(1).Prior clinical studies have identified adverse events(1,2), and remdesivir has been shown to inhibit mitochondrial RNA polymerase in biochemical experiments(7), 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 transporter SLC29A3 mitigates remdesivir toxicity without a commensurate decrease in SARS-CoV-2 antiviral potency and that the mitochondrial adenylate kinase AK2 is a remdesivir kinase required for remdesivir efficacy and toxicity. This work elucidates the cellular mechanisms of remdesivir metabolism and provides a candidate gene target to reduce remdesivir cytotoxicity. äElucidation of remdesivir cytotoxicity pathways through genome-wide CR(epmc).pdf DeepDyve Pubget Overpricing