SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication
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Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first detected in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. Here we show detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection and provide evidence for their nuclease resistance and protection by cellular membranes suggesting that detection of subgenomic RNAs in such samples may not be a suitable indicator of active coronavirus replication/infection.
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The discontinuous mechanism of coronavirus transcription is confirmed by sequencing the subgenomic RNAs from cultured viruses.
“This discontinuous mechanism of transcription [26,61] is confirmed by sequencing the subgenomic RNAs from cultured viruses (Figure 4C).”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [26]
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- Authors
- Alexandersen, S., Chamings, A., & Bhatta, T. R.
- Affiliations
- Deakin University (AU)
- Venue
- Nature Communications
- Published
- 2020-11-27
- Volume
- 11
- Issue
- 1
- Pages
- 6059-6059
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7695715
- OpenAlex
- W3107258715
- Cited by
- 305
- References
- 7
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 41 · 2023: 51 · 2022: 86 · 2021: 83 · 2020: 11
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Deakin University (NA)
- Department of Health | National Health and Medical Research Council (GNT9000413)
- Barwon Health
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, subgenomic RNA, viral RNA replication, viral transcription, diagnostic samples, nuclease resistance, double-membrane vesicles, coronavirus infection
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Testing, Adult, Cytoplasm, Female, Humans, Male, Middle Aged, Nasopharynx, Oropharynx, RNA, Viral, Time Factors, Virus Replication, Polymerase Chain Reaction, Genome, Viral, Host-Pathogen Interactions, Young Adult, High-Throughput Nucleotide Sequencing
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