Coronavirus genomic RNA packaging

Masters, Paul S.

doi:10.1016/j.virol.2019.08.031

Cited by 227 publications

(244 citation statements)

References 75 publications

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“…We first analyzed the effects of three mid-sized viral RNA fragments: (1) 5'-400, containing the 400 nt at the 5' end of the SARS-CoV-2 genome, which is thought to include multiple secondary structure elements and the leader TRS 51-53 ; (2) PS-318, a sequence near the end of ORF1b in SARS-CoV, proposed as a packaging sequence 54,55 but of unknown function 51,56 At 10 µM N protein, the three viral RNAs rapidly generated branched networks of liquid-like beads. Higher N protein concentrations produced large liquid-like droplets several microns in diameter.…”

Section: N Protein Of Sars-cov-2 Forms Rna-dependent Biomolecular Conmentioning

confidence: 99%

Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein

Carlson

Asfaha

Ghent

et al. 2020

Preprint

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The nucleocapsid (N) protein of coronaviruses serves two major functions: compaction of the RNA genome in the virion and regulation of viral gene transcription in the infected cell1–3. The N protein contains two globular RNA-binding domains surrounded by regions of intrinsic disorder4. Phosphorylation of the central disordered region is required for normal viral genome transcription5,6, which occurs in a cytoplasmic structure called the replication transcription complex (RTC)7–11. It is not known how phosphorylation controls N protein function. Here we show that the N protein of SARS-CoV-2, together with viral RNA, forms biomolecular condensates12–15. Unmodified N protein forms partially ordered gel-like structures that depend on multivalent RNA-protein and protein-protein interactions. Phosphorylation reduces a subset of these interactions, generating a more liquid-like droplet. We speculate that distinct oligomeric states support the two functions of the N protein: unmodified protein forms a structured oligomer that is suited for nucleocapsid assembly, and phosphorylated protein forms a liquid-like compartment for viral genome processing. Inhibitors of N protein phosphorylation could therefore serve as antiviral therapy.

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Section: N Protein Of Sars-cov-2 Forms Rna-dependent Biomolecular Conmentioning

confidence: 99%

Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein

Carlson

Asfaha

Ghent

et al. 2020

Preprint

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“…The SL2 is more conserved between the three viruses than SL1, and the top of SL2 is featured with a hexaloop that contains a Urich motif. It should be noted that genomic PSs for different CoVs consist of RNA structure elements that vary in length and location in the genome of viruses within the same lineages (14,31). For example, the genomic PS of MERS-CoV which is a lineage C betacoronavirus was identified in a similar position as the SARS-CoV at the 3' end of the ORF1ab region (21).…”

Section: Discussionmentioning

confidence: 99%

In silicoidentification of conservedcis-acting RNA elements in the SARS-CoV-2 genome

Alhatlani

2020

Preprint

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Aim: The aim of this study was to computationally predict conserved RNA sequences and structures known as cis-acting RNA elements (CREs) located within the SARS-CoV-2 genome. Materials & methods: Bioinformatics tools were used to analyse and predict cisacting regulatory elements by obtaining viral sequences from available databases. Results: Computational analysis prediction revealed the presence of RNA stem-loop structures within the 3' end of the ORF1ab region that are analogous to the previously identified SARS-CoV genomic packaging signals. Alignment-based RNA secondary structures prediction of the 5' end of the SARS-CoV-2 genome identified also conserved CREs. Conclusion: These CREs could be used as potential targets for a vaccine and/or antiviral therapeutics developments; however, further studies would be required to confirm their roles in the SARS-CoV-2 life cycle.

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“…There are three important parameters for coronavirus genome packaging -a) viral infection includes not only replication of gRNA but also the formation of subgenomic (sg) RNAs which act as mRNAs for genes present downstream, b) coronaviruses have helically symmetric icosahedral nucleocapsids (Masters, 2006;Neuman et al, 2006;Gui et al, 2017) which is simply not common for a positive-strand RNA virus and c) the arrangement of the nucleocapsid into the virion initiates via interactions between the -C terminal of multiple monomers of N and M proteins (Escors et al, 2001& Masters, 2019. The packaging of coronavirus is quite a challenge to obtain a specific recognition and selection of gRNAs and other RNA species (Masters, 2019).…”

Section: Genomic Compositionmentioning

confidence: 99%

A Coadunation of Biological and Mathematical Perspectives on the Pandemic COVID-19: A Review

Qazi¹,

Sheikh²,

Faheem³

et al. 2020

Preprint

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Coronaviruse disease (COVID-19) outbreak has created an emergency globally, and social distancing and isolation is the only solution to prevent its spread. Several countries have announced fully locked on to tackle this pandemic. The recent COVID-2019 has shaken the globe with incidence cases of more than half-million cases, and a mortality toll of more than twenty thousand to date. The coronavirus family is inclusive of pathogen of both – animal species and humans, encapsulating the isolated severe acute respiratory syndrome coronavirus (SARS-CoV). Researchers round the globe have been dexterously working to decode this lethal virus. Many mathematical frameworks have also been depicted which have helped to understand the dynamics of the COVID-19. Research on coronaviruses continues to explore various aspects of viral replication and pathogenesis to understanding the predilection of these viruses to switch between species, to develop an infection in a new host, and to identify significant reservoirs of coronaviruses will dramatically aid in our potential to prophesize when and where potential epidemics may occur. Many of the non-structural and accessory proteins encoded by the viruses remain unclear and unknown. This systematic review highlights the current situation of the pandemic, virus genomic composition, pathogenesis, symptomatology, diagnosis, and prognosis along with mathematical models of disease transmission and dynamics.

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Coronavirus genomic RNA packaging

Cited by 227 publications

References 75 publications

Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein

Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein

In silicoidentification of conservedcis-acting RNA elements in the SARS-CoV-2 genome

A Coadunation of Biological and Mathematical Perspectives on the Pandemic COVID-19: A Review

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