The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir.
iScience
; 24(8): 102857, 2021 Aug 20.
Article
in English
| MEDLINE | ID: covidwho-1309256
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive single-stranded RNA virus, causes the coronavirus disease 19 pandemic. During the viral replication and transcription, the RNA-dependent RNA polymerase "jumps" along the genome template, resulting in discontinuous negative-stranded transcripts. Although the sense-mRNA architectures of SARS-CoV-2 were reported, its negative 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 with variable transcription efficiency for different genes. During negative strand synthesis, numerous non-canonical fusion transcripts are also 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 antiviral vaccine development and drug design.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Topics:
Vaccines
Language:
English
Journal:
IScience
Year:
2021
Document Type:
Article
Affiliation country:
J.isci.2021.102857
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