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The Strand-biased Transcription of SARS-CoV-2 and Unbalanced Inhibition by Remdesivir (preprint)
biorxiv; 2020.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2020.10.15.325050
ABSTRACT
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.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Main subject:
COVID-19
Language:
English
Year:
2020
Document Type:
Preprint
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