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The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir
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-stra...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277956/ https://www.ncbi.nlm.nih.gov/pubmed/34278249 http://dx.doi.org/10.1016/j.isci.2021.102857 |
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author | Zhao, Yan Sun, Jing Li, Yunfei Li, Zhengxuan Xie, Yu Feng, Ruoqing Zhao, Jincun Hu, Yuhui |
author_facet | Zhao, Yan Sun, Jing Li, Yunfei Li, Zhengxuan Xie, Yu Feng, Ruoqing Zhao, Jincun Hu, Yuhui |
author_sort | Zhao, Yan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8277956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82779562021-07-14 The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir Zhao, Yan Sun, Jing Li, Yunfei Li, Zhengxuan Xie, Yu Feng, Ruoqing Zhao, Jincun Hu, Yuhui iScience Article 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. Elsevier 2021-07-14 /pmc/articles/PMC8277956/ /pubmed/34278249 http://dx.doi.org/10.1016/j.isci.2021.102857 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Zhao, Yan Sun, Jing Li, Yunfei Li, Zhengxuan Xie, Yu Feng, Ruoqing Zhao, Jincun Hu, Yuhui The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir |
title | The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir |
title_full | The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir |
title_fullStr | The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir |
title_full_unstemmed | The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir |
title_short | The strand-biased transcription of SARS-CoV-2 and unbalanced inhibition by remdesivir |
title_sort | strand-biased transcription of sars-cov-2 and unbalanced inhibition by remdesivir |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277956/ https://www.ncbi.nlm.nih.gov/pubmed/34278249 http://dx.doi.org/10.1016/j.isci.2021.102857 |
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