Author: Zhao, Yan; Sun, Jing; Li, Yunfei; Li, Zhengxuan; Xie, Yu; Feng, Ruoqing; Zhao, Jincun; Hu, Yuhui
Title: The Strand-biased Transcription of SARS-CoV-2 and Unbalanced Inhibition by Remdesivir Cord-id: 1d9z8h72 Document date: 2020_10_15
ID: 1d9z8h72
Snippet: SARS-CoV-2, a positive single-stranded RNA virus, caused the COVID-19 pandemic. Although its sense-mRNA architecture was reported, its anti-sense strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand. During negative strand synthesis, apart from canonical sub-genomic ORFs, numerous non-canonical fusion transcripts are formed, driven by 3-15 nt sequence homology scattered along the genome but more prone
Document: SARS-CoV-2, a positive single-stranded RNA virus, caused the COVID-19 pandemic. Although its sense-mRNA architecture was reported, its anti-sense strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand. During negative strand synthesis, apart from canonical sub-genomic ORFs, numerous non-canonical fusion transcripts are formed, driven by 3-15 nt sequence homology scattered along the genome but more prone to be inhibited by SARS-CoV-2 RNA polymerase inhibitor Remdesivir. The drug also represses more of the negative than the positive strand synthesis as supported by a mathematic simulation model and experimental quantifications. Overall, this study opens new sights into SARS-CoV-2 biogenesis and may facilitate the anti-viral drug design. One Sentence Summary Strand-biased transcription of SARS-CoV-2.
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