Coronavirus biology and replication: implications for SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2020, Volume and Issue: 19(3), P. 155 - 170

Published: Oct. 28, 2020

The SARS-CoV-2 pandemic and its unprecedented global societal economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into human population. Although previous SARS-CoV MERS-CoV epidemics raised awareness need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. development effective intervention strategies relies on knowledge molecular cellular mechanisms infections, which highlights significance studying virus-host interactions at level identify targets antiviral elucidate critical viral host determinants that decisive severe disease. In this Review, we summarize first discoveries shape our current understanding infection throughout intracellular life cycle relate biology. elucidation similarities differences between other coronaviruses will support future preparedness combat infections.

Language: Английский

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The Architecture of SARS-CoV-2 Transcriptome

Cell, Journal Year: 2020, Volume and Issue: 181(4), P. 914 - 921.e10

Published: April 23, 2020

Language: Английский

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Nanopore sequencing technology, bioinformatics and applications

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 39(11), P. 1348 - 1365

Published: Nov. 1, 2021

Language: Английский

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Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein

Genome Medicine, Journal Year: 2020, Volume and Issue: 12(1)

Published: July 28, 2020

SARS-CoV-2 is a recently emerged respiratory pathogen that has significantly impacted global human health. We wanted to rapidly characterise the transcriptomic, proteomic and phosphoproteomic landscape of this novel coronavirus provide fundamental description virus's genomic potential.

Language: Английский

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Structures and functions of coronavirus replication–transcription complexes and their relevance for SARS-CoV-2 drug design

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 21 - 39

Published: Nov. 25, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions of people and continues to cause massive global upheaval. Coronaviruses are positive-strand RNA viruses with an unusually large genome ~30 kb. They express RNA-dependent polymerase a cohort other replication enzymes supporting factors transcribe replicate their genomes. The proteins performing these essential processes prime antiviral drug targets, but discovery is hindered by our incomplete understanding synthesis processing. In infected cells, the must coordinate viral host produce both mRNAs new Recent research aiming decipher contextualize structures, functions interplay subunits SARS-CoV-2 transcription complex burgeoned. this Review, we discuss recent advancements in molecular basis complexity RNA-synthesizing machinery. Specifically, outline mechanisms regulation translation, transcription. We also composition complexes suitability as targets for therapy. coronaviruses rely on specialized studies have improved transcription, offer therapeutic targets.

Language: Английский

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Detection of Plant Viruses and Disease Management: Relevance of Genetic Diversity and Evolution

Frontiers in Plant Science, Journal Year: 2020, Volume and Issue: 11

Published: July 17, 2020

Plant viruses cause considerable economic losses and are a threat for sustainable agriculture. The frequent emergence of new viral diseases is mainly due to international trade, climate change the ability rapid evolution. Disease control based on two strategies: i) immunization (genetic resistance obtained by plant breeding, transformation, cross-protection, or others), ii) prophylaxis restrain virus dispersion (using quarantine, certification, removal infected plants, natural vectors, other procedures). management relies strongly fast accurate identification causal agent. For known viruses, diagnosis consists in assigning infecting sample group sharing common characteristics, which usually referred as species. However, specificity can also reach higher taxonomic levels, genus family, lower strain variant. Diagnostic procedures must be optimized accuracy detecting maximum number members within (sensitivity true positive rate) distinguishing them from outgroup (specificity negative rate). This requires information genetic relationships within-group with groups. influence diversity populations disease well documented, but how integrate detection methods still scarce. Here we review techniques used control, including characteristics such accuracy, level, multiplexing, quantification, portability designability. effect evolution design performance some discussed. High-throughput next-generation sequencing provides broad-spectrum enabling multiplex detection, quantification discovery viruses. Likely, this technique will future standard diagnostics its cost dropping becoming more affordable.

Language: Английский

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Mapping the epigenetic modifications of DNA and RNA

Protein & Cell, Journal Year: 2020, Volume and Issue: 11(11), P. 792 - 808

Published: May 22, 2020

Abstract Over 17 and 160 types of chemical modifications have been identified in DNA RNA, respectively. The interest understanding the various biological functions RNA has lead to cutting-edged fields epigenomics epitranscriptomics. Developing tools detect specific genome or transcriptome greatly facilitated their study. Here, we review recent technological advances this rapidly evolving field. We focus on high-throughput detection methods findings for these modifications, discuss questions be addressed as well. also summarize third-generation sequencing methods, which enable long-read single-molecule modification.

Language: Английский

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On the origin and evolution of SARS-CoV-2

Experimental & Molecular Medicine, Journal Year: 2021, Volume and Issue: 53(4), P. 537 - 547

Published: April 1, 2021

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global outbreak of a disease (herein referred to as COVID-19). Other viruses in same phylogenetic group have been previous regional outbreaks, including SARS and MERS. SARS-CoV-2 has zoonotic origin, similar causative these outbreaks. repetitive introduction animal into human populations resulting outbreaks suggests that future epidemics are inevitable. Therefore, understanding molecular origin evolution will provide critical insights preparing preventing A key feature its propensity genetic recombination across host species boundaries. Consequently, genome harbors signatures multiple events, likely encompassing broad geographic regions. regions show impact purifying selection. spike (S) protein SARS-CoV-2, which enables virus enter cells, exhibits both selection ancestral leading an effective S capable infecting many other mammalian cells. spread explosive growth population (within hosts) contributed additional mutational variability this genome, increasing opportunities recombination.

Language: Английский

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Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy

iScience, Journal Year: 2021, Volume and Issue: 24(3), P. 102151 - 102151

Published: Feb. 7, 2021

Detailed knowledge of the molecular biology severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial for understanding viral replication, host responses, and disease progression. Here, we report gene expression profiles three SARS-CoV- SARS-CoV-2-infected human cell lines. SARS-CoV-2 elicited an approximately two-fold higher stimulation innate immune response compared to SARS-CoV in epithelial line Calu-3, including induction miRNA-155. Single-cell RNA sequencing infected cells showed that genes induced by virus infections were broadly upregulated, whereas interferon beta/lambda genes, a pro-inflammatory cytokines such as IL-6, expressed only small subsets cells. Temporal analysis suggested transcriptional activities regulatory factors precede those nuclear factor κB. Lastly, identified heat shock protein 90 (HSP90) relevant infection. Inhibition HSP90 activity resulted reduction replication cytokine primary airway

Language: Английский

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Next generation sequencing of SARS-CoV-2 genomes: challenges, applications and opportunities

Briefings in Bioinformatics, Journal Year: 2020, Volume and Issue: 22(2), P. 616 - 630

Published: Oct. 8, 2020

Various next generation sequencing (NGS) based strategies have been successfully used in the recent past for tracing origins and understanding evolution of infectious agents, investigating spread transmission chains outbreaks, as well facilitating development effective rapid molecular diagnostic tests contributing to hunt treatments vaccines. The ongoing COVID-19 pandemic poses one greatest global threats modern history has already caused severe social economic costs. efficient methods reconstruct genomic sequence SARS-CoV-2, etiological agent COVID-19, fundamental design devise measures mitigate diffusion pandemic. Diverse approaches can, testified by number available sequences, be applied SARS-CoV-2 genomes. However, each technology approach its own advantages limitations. In current review, we will provide a brief, but hopefully comprehensive, account currently platforms methodological We also present an outline repositories databases that access data associated metadata. Finally, offer general advice guidelines appropriate sharing deposition metadata, suggest more standardized integration future SARS-CoV-2-related would greatly facilitate struggle against this new pathogen. hope our 'vademecum' production handling data, contribute objective.

Language: Английский

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