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

Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa DOI Creative Commons
Raquel Viana, Sikhulile Moyo, Daniel G. Amoako

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 679 - 686

Published: Jan. 7, 2022

Abstract The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. first was associated with a mix of lineages, while the second and third waves were driven Beta (B.1.351) Delta (B.1.617.2) variants, respectively 1–3 . In November 2021, genomic surveillance teams South Botswana detected new variant rapid resurgence infections Gauteng province, Africa. Within days genome being uploaded, it designated concern (Omicron, B.1.1.529) World Health Organization and, within weeks, had identified 87 countries. Omicron is exceptional for carrying over 30 mutations spike glycoprotein, which are predicted to influence antibody neutralization function 4 Here we describe profile early transmission dynamics Omicron, highlighting spread regions high levels population immunity.

Language: Английский

Citations

1622

SARS-CoV-2 variant biology: immune escape, transmission and fitness DOI Creative Commons
Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Language: Английский

Citations

1020

SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo DOI Open Access
Kenrie P. Y. Hui,

John Chi Wang Ho,

Man Chun Cheung

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 715 - 720

Published: Feb. 1, 2022

Language: Английский

Citations

767

Probable Transmission of SARS-CoV-2 Omicron Variant in Quarantine Hotel, Hong Kong, China, November 2021 DOI Creative Commons
Haogao Gu,

Pavithra Krishnan,

Daisy Y.M. Ng

et al.

Emerging infectious diseases, Journal Year: 2021, Volume and Issue: 28(2), P. 460 - 462

Published: Dec. 3, 2021

We report detection of severe acute respiratory syndrome coronavirus 2 Omicron variant (B.1.1.529) in an asymptomatic, fully vaccinated traveler a quarantine hotel Hong Kong, China. The was also detected staying room across the corridor from index patient, suggesting transmission despite strict precautions.

Language: Английский

Citations

180

The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape, and vaccine effectivity DOI Open Access

Yongbing Zhou,

Hui‐Lin Zhi,

Yong Teng

et al.

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Sept. 13, 2022

As of November 2021, several SARS-CoV-2 variants appeared and became dominant epidemic strains in many countries, including five concern (VOCs) Alpha, Beta, Gamma, Delta, Omicron defined by the World Health Organization during COVID-19 pandemic. August 2022, is classified into main lineages, BA.1, BA.2, BA.3, BA.4, BA.5 some sublineages (BA.1.1, BA.2.12.1, BA.2.11, BA.2.75, BA.4.6) (https://www.gisaid.org/). Compared to previous VOCs (Alpha, Delta), all lineages have most highly mutations spike protein, with 50 accumulated throughout genome. Early data indicated that BA.2 sublineage had higher infectivity more immune escape than early wild-type (WT) strain, VOCs, BA.1. Recently, global surveillance suggest a transmissibility BA.4/BA.5 BA.1.1 becoming strain countries globally.

Language: Английский

Citations

133

Animal models in SARS-CoV-2 research DOI Open Access
Hin Chu, Jasper Fuk‐Woo Chan, Kwok‐Yung Yuen

et al.

Nature Methods, Journal Year: 2022, Volume and Issue: 19(4), P. 392 - 394

Published: April 1, 2022

Language: Английский

Citations

90

Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant DOI
Vineet Sharma, Himanshu Rai, Dev Nath Singh Gautam

et al.

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(5), P. 1876 - 1885

Published: Jan. 27, 2022

COVID's Omicron variant has sparked a slew of concerns across the globe. This review aims to provide brief overview what we know about right now. The new been discovered in 149 countries all six World Health Organization (WHO) regions since its discovery South Africa on November 24, 2021 and became dominant country less than 3 weeks. WHO warned that B.1.1.529 is spreading at an unprecedented rate, urged prepare for worst. Over course this time, researchers from around world have uncovered wealth information virus's epidemiology biological properties. Case numbers are increasing exponentially hard-hit areas such as Africa, United Kingdom, USA (overtaking delta variant), implying highly transmissible. Initial research provided some insights into efficacy vaccines against whether it produces major illness, however, much remains unknown, additional work needed investigate initial reports represent real-world situations.

Language: Английский

Citations

78

Replication of SARS-CoV-2 Omicron BA.2 variant in ex vivo cultures of the human upper and lower respiratory tract DOI
Kenrie P. Y. Hui, Ka‐Chun Ng,

John CW Ho

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 83, P. 104232 - 104232

Published: Aug. 18, 2022

Language: Английский

Citations

77

Phase separation by the SARS-CoV-2 nucleocapsid protein: Consensus and open questions DOI Creative Commons
Sean M. Cascarina, Eric D. Ross

Journal of Biological Chemistry, Journal Year: 2022, Volume and Issue: 298(3), P. 101677 - 101677

Published: Feb. 4, 2022

In response to the recent SARS-CoV-2 pandemic, a number of labs across world have reallocated their time and resources better our understanding virus. For some viruses, including SARS-CoV-2, viral proteins can undergo phase separation: biophysical process often related partitioning protein RNA into membraneless organelles in vivo. this review, we discuss emerging observations separation by nucleocapsid (N) protein—an essential required for replication—and possible vivo functions that been proposed N-protein separation, replication, genomic packaging, modulation host-cell infection. Additionally, since relatively large studies examining published short span time, take advantage situation compare results from similar experiments studies. Our evaluation highlights potential strengths pitfalls drawing conclusions single set experiments, as well value publishing overlapping scientific performed simultaneously multiple labs. virus responsible COVID-19 ongoing has exacted an enormous toll on human health, with >5.6 million deaths >350 infections currently attributed (according World Health Organization data, https://covid19.who.int/, accessed 1/26/22). The pandemic had already led estimated $16 trillion global economic costs October 2020 (1Cutler D.M. Summers L.H. virus.JAMA. 2020; 324: 1495-1496Google Scholar) disrupted nearly every sector, science. Over past year half, extraordinary progress made improving novel Emerging experimental implicate critical factor mediating (gRNA) Intriguingly, N ability (PS), which is now considered pervasive phenomenon organizing broad diversity biological processes cells. models, results, PS protein. given remarkable publications topic within ∼ 1 year, leverage unusual evaluate how work, parallel independent groups, may shape resulting conclusions. practice, science sequentially: one discovery typically precedes, informs, directs subsequent experimentation. incentive structure science, rewards novelty, promotes sequential model, disincentivizes focused replication validation. One limitation model subtle differences design sometimes significant impact thus influence direction experiments. However, publication was punctuated pandemic. Many historically little or no prior experience virology applied respective areas expertise questions SARS-CoV-2. 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Lei Crispin et al.Molecular architecture virus.Cell. 183: 730-738.e13Google 5Cao Cai Xiao Rao Hu Yang Xing Wang Li Zhou Xue genome inside virion.Nat. 2021; 12: 3917Google Locally RNPs be further organized more complex arrangements clustering particular stoichiometries geometries Scholar), although other evidence models SARS-CoV linear, helical RNP arrangement 6Filho H.V.R. Jara G.E. Batista F.A.H. Schleder G.R. Tonoli C.C. Soprano A.S. Guimarães Borges A.C. Cassago A. Bajgelman M.C. Marques R.E. Trivella D.B.B. Franchini K.G. Figueira A.C.M. Benedetti C.E. al.Structural dynamics induced binding.bioRxiv. ([preprint])https://doi.org/10.1101/2021.08.27.457964Google These preferentially accumulate curved membranes indicating either association aids curvature during virion formation, are preferred recruitment surface RNPs. also interacts luminal domain (i.e., interior virions) M protein, mechanism N-containing ERGIC (7Lu Ye Q. Singh Cao Diedrich J.K. Yates J.R. Villa E. Cleveland D.W. Corbett K.D. phosphoprotein mutually exclusive condensates membrane-associated protein.Nat. 502Google Some suggests both interact E (8Tseng Y.-T. S.-M. K.-J. C.-T. palmitoylation nucleocapid not promoting virus-like particle production.J. Biomed. Sci. 21: 34Google 9Li Guo Tian Liu Qu Yin Zhu Peng al.Virus-host interactome proteomic survey reveal virulence factors influencing pathogenesis.Med. (N. Y.). 2: 99-112.e7Google While precise detail regarding interactions individual molecules intact still forthcoming, clearly plays central role compaction organization virions. involves two distinct yet coexisting phases well-mixed solution: dense high concentration dilute low (10Banani S.F. Lee H.O. Hyman A.A. Rosen M.K. Biomolecular condensates: Organizers cellular biochemistry.Nat. Rev. Mol. Cell Biol. 2017; 18: 285-298Google Subsequent initial PS, additional transitions change material properties (11Patel Jawerth Maharana Jahnel Hein M.Y. Stoynov Mahamid Saha Franzmann T.M. 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Polyphasic linkage ligand regulation biomolecular condensates.Biophys. 2021302Google system, driven homotypic between identical biopolymers), whereas co-PS system heterotypic different biopolymers) combination interactions. type multivalent observe certain appear common among known separate. example, separating contain RNA-binding domains, intrinsically disordered (IDRs), oligomerization low-complexity domains. gained attention biology due connection “biomolecular condensates” 13Boeynaems 16Hyman Weber C.A. Jülicher Liquid-liquid biology.Annu. Dev. 30: 39-58Google enriched nucleic acids. Much like observed vitro, consist network (often acids, proteins, biopolymers). types described, (but limited to) granules, P-bodies, nucleoli, nuclear speckles, germ Cajal bodies Each condensate sets constituent properties, functions, stability, regulation. Regardless differences, condensation represents elegant solution concentrating groups regulatable sensitive fashion. 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Stanley Schaletzky Yildiz RNA.PLoS 19e3001425Google 29Savastano Ibáñez de Opakua Rankovic Zweckstetter Nucleocapsid RNA-rich polymerase-containing condensates.Nat. 6041Google 30Carlson C.R. Asfaha J.B. Ghent C.M. Howard Hartooni Safari Frankel A.D. Morgan D.O. Phosphoregulation basis dual functions.Mol. 1092-1103.e4Google 31Luo Zhao Ma Jin He Zou Liang Chi al.SARS-CoV-2 G3BPs disassemble facilitate production.Sci. Bull. 66: 1194-1204Google 32Perdikari Murthy Ryan V.H. Watters Naik M.T. phase-separates hnRNPs.EMBO 39e106478Google 33Wang undergoes through N-terminal region.Cell 5Google 34Wu Zhuang Xie Cui RNA-induced facilitates NF-κB hyper-activation inflammation.Signal Transduct. Target. Ther. 6: 167Google 35Chen P.H. Liquid–liquid RNA.Cell 1143-1145Google 36Zhao Ge Yuan Xiong Feng Shu Lang al.Understanding characteristics provides therapeutic opportunity against SARS-CoV-2.Protein 734-740Google Figure affecting vitro vivo, each discussed sections. purported and, broadly, learned “consensus” view timeframe. We note while done best faithfully interpret available all present rigorous quantification methods differed studies; therefore, based least degree subjective interpretation. containing prion-like (37Fomicheva prions granules: Defining compositional promote assemblies.Int. 22: 1251Google 38March Z.M. King O.D. Prion-like epigenetic regulators, scaffolds subcellular organization, drivers neurodegenerative disease.Brain 2016; 1647: 9-18Google 39Harrison A.F. health disease.Biochem. 474: 1417-1438Google itself capable undergoing (40Van Treeck Protter D.S.W. Matheny Khong Link C.D. Parker self-assembly contributes defining transcriptome.Proc. Natl. Acad. 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RNAs varying lengths sequences degrees, suggesting somewhat nonspecific (though N+RNA greater sequence specificity, later section). tested wide range concentrations, exceedingly amounts tended inhibit re-entrant imbalance Electrostatic consistently implicated regulating RNA-dependent 1Aii). salt salts used (48Alberti Considerations challenges studying liquid-liquid condensates.Cell. 176: 419-434Google generally presumed reflect electrostatic PS. Lower enhanced (20Zhao throu

Language: Английский

Citations

73

Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa DOI Creative Commons
Raquel Viana, Sikhulile Moyo, Daniel G. Amoako

et al.

Nature, Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 7, 2022

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. first was associated with a mix of lineages, while the second and third waves were driven Beta (B.1.351) Delta (B.1.617.2) variants, respectively1–3. In November 2021, genomic surveillance teams South Botswana detected new variant rapid resurgence infections Gauteng province, Africa. Within days genome being uploaded, it designated concern (Omicron, B.1.1.529) World Health Organization and, within weeks, had identified 87 countries. Omicron is exceptional for carrying over 30 mutations spike glycoprotein, which are predicted to influence antibody neutralization function4. Here we describe profile early transmission dynamics Omicron, highlighting spread regions high levels population immunity. strain SARS-CoV-2.

Language: Английский

Citations

71