Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding DOI Creative Commons
Helder Veras Ribeiro Filho, Gabriel Ernesto Jara, Fernanda Aparecida Heleno Batista

et al.

PLoS Computational Biology, Journal Year: 2022, Volume and Issue: 18(5), P. e1010121 - e1010121

Published: May 12, 2022

The nucleocapsid (N) protein of the SARS-CoV-2 virus, causal agent COVID-19, is a multifunction phosphoprotein that plays critical roles in virus life cycle, including transcription and packaging viral RNA. To play such diverse roles, N has two globular RNA-binding modules, N- (NTD) C-terminal (CTD) domains, which are connected by an intrinsically disordered region. Despite wealth structural data available for isolated NTD CTD, how these domains arranged full-length oligomerization influences its activity remains largely unclear. Herein, using experimental from electron microscopy biochemical/biophysical techniques combined with molecular modeling dynamics simulations, we show that, absence RNA, formed structurally dynamic dimers, CTD extended conformations. However, presence assumed more compact conformation where packed together. We also provided octameric model bound to RNA consistent images Together, our results shed new light on higher-order oligomeric structure this versatile protein.

Language: Английский

Molecular Evolution of SARS-CoV-2 during the COVID-19 Pandemic DOI Open Access
Luis Daniel González-Vázquez, Miguel Arenas

Genes, Journal Year: 2023, Volume and Issue: 14(2), P. 407 - 407

Published: Feb. 4, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well resistance to monoclonal antibodies polyclonal sera, among other treatments. In order understand causes consequences observed SARS-CoV-2 diversity, a variety studies investigated evolution this virus humans. general, evolves with moderate rate evolution, 10

Language: Английский

Citations

30
Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection DOI Creative Commons
Xiaoyuan Lin,

Beibei Fu,

Yan Xiong

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(1), P. e1011128 - e1011128

Published: Jan. 23, 2023

Coronavirus disease 2019 is a respiratory infectious caused by the severe acute syndrome coronavirus 2 (SARS-CoV-2). Evidence on pathogenesis of SARS-CoV-2 accumulating rapidly. In addition to structural proteins such as Spike and Envelope, functional roles non-structural accessory in regulating viral life cycle host immune responses remain be understood. Here, we show that open reading frame 8 (ORF8) acts messenger for inter-cellular communication between alveolar epithelial cells macrophages during infection. Mechanistically, ORF8 secretory protein can secreted infected via both conventional unconventional pathways. Conventionally glycosylated loses ability recognize interleukin 17 receptor A macrophages, possibly due steric hindrance imposed N-glycosylation at Asn78. However, unconventionally does not undergo glycosylation without experiencing ER-Golgi trafficking, thereby activating downstream NF-κB signaling pathway facilitating burst cytokine release. Furthermore, deletion attenuates inflammation yields less lung lesions hamsters. Our data collectively highlights role development storms

Language: Английский

Citations

23
Targeted accurate RNA consensus sequencing (tARC-seq) reveals mechanisms of replication error affecting SARS-CoV-2 divergence DOI
Catherine C. Bradley, Chen Wang,

Alasdair J.E. Gordon

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(5), P. 1382 - 1392

Published: April 22, 2024

Language: Английский

Citations

12
Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion DOI Creative Commons
Harriet V Mears, George R. Young, Theo Sanderson

et al.

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(1), P. e3002982 - e3002982

Published: Jan. 21, 2025

Coronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5′ genomic leader upstream each body open reading frame. In SARS-CoV-2, TRS has consensus AAACGAAC; upon searching for emergence this motif global SARS-CoV-2 sequences, we find that it evolves frequently, especially 3′ end genome. We show well-supported examples Spike gene—within nsp16 coding region ORF1b—which expressed during human infection, canonical Envelope gene TRS, both which have evolved convergently multiple lineages. The most frequent neo-TRS within Nucleocapsid gene, present virtually all viruses from B.1.1 lineage, including variants concern Alpha, Gamma, Omicron descendants thereof. Here, demonstrate leads to expression novel mRNA encoding truncated C-terminal portion Nucleocapsid, an antagonist type I interferon production contributes viral fitness infection. observe distinct phenotypes when sequence mutated compared alone ablated. Our findings undergoing evolutionary changes at functional RNA level addition amino acid level.

Language: Английский

Citations

1
Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding DOI Creative Commons
Helder Veras Ribeiro Filho, Gabriel Ernesto Jara, Fernanda Aparecida Heleno Batista

et al.

PLoS Computational Biology, Journal Year: 2022, Volume and Issue: 18(5), P. e1010121 - e1010121

Published: May 12, 2022

The nucleocapsid (N) protein of the SARS-CoV-2 virus, causal agent COVID-19, is a multifunction phosphoprotein that plays critical roles in virus life cycle, including transcription and packaging viral RNA. To play such diverse roles, N has two globular RNA-binding modules, N- (NTD) C-terminal (CTD) domains, which are connected by an intrinsically disordered region. Despite wealth structural data available for isolated NTD CTD, how these domains arranged full-length oligomerization influences its activity remains largely unclear. Herein, using experimental from electron microscopy biochemical/biophysical techniques combined with molecular modeling dynamics simulations, we show that, absence RNA, formed structurally dynamic dimers, CTD extended conformations. However, presence assumed more compact conformation where packed together. We also provided octameric model bound to RNA consistent images Together, our results shed new light on higher-order oligomeric structure this versatile protein.

Language: Английский

Citations

37