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

Global landscape of SARS-CoV-2 mutations and conserved regions DOI Creative Commons
Mohammad Hadi Abbasian, Mohammadamin Mahmanzar, Karim Rahimian

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 25, 2023

Abstract Background At the end of December 2019, a novel strain Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been identified in Wuhan, central city China, and then spread to every corner globe. As October 8, 2022, total number COVID-19 cases had reached over 621 million worldwide, with more than 6.56 confirmed deaths. Since SARS-CoV-2 genome sequences change due mutation recombination, it is pivotal surveil emerging variants monitor changes for improving pandemic management. Methods 10,287,271 sequence samples were downloaded FASTA format from GISAID databases February 24, 2020, April 2022. Python programming language (version 3.8.0) software was utilized process files identify conservation. The NCBI RefSeq (accession no. NC_045512.2) considered as reference sequence. Results Six mutations 50% frequency global SARS-CoV-2. These include P323L (99.3%) NSP12, D614G (97.6) S, T492I (70.4) NSP4, R203M (62.8%) N, T60A (61.4%) Orf9b, P1228L (50.0%) NSP3. In genome, no observed 90% nsp11, nsp7, nsp10, nsp9, nsp8, nsp16 regions. On other hand, nsp3, nsp4, nsp12, M maximum rate mutations. S protein, highest aa 508–635(0.77%) 381–508 (0.43%). 66–88 (2.19%), 7–14, 164–246 (2.92%) M, E, N proteins, respectively. Conclusion Therefore, monitoring proteomic detecting hot spots conserved regions could be applied improve SARS‐CoV‐2 diagnostic efficiency design safe effective vaccines against variants.

Language: Английский

Citations

63
Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States DOI Creative Commons
Aijing Feng, Sarah N. Bevins,

Jeff Chandler

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 10, 2023

Abstract SARS-CoV-2 is a zoonotic virus with documented bi-directional transmission between people and animals. Transmission of from humans to free-ranging white-tailed deer ( Odocoileus virginianus ) poses unique public health risk due the potential for reservoir establishment where variants may persist evolve. We collected 8,830 respiratory samples across Washington, D.C. 26 states in United States November 2021 April 2022. obtained 391 sequences identified 34 Pango lineages including Alpha, Gamma, Delta, Omicron variants. Evolutionary analyses showed these viruses originated at least 109 independent spillovers humans, which resulted 39 cases subsequent local deer-to-deer three spillover back humans. Viruses repeatedly adapted recurring amino acid substitutions spike other proteins. Overall, our findings suggest that multiple were introduced, became enzootic, co-circulated deer.

Language: Английский

Citations

52
TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence DOI Creative Commons

Jiang Ren,

Shuai Wang, Zhi Zong

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 4, 2024

Abstract Viruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected host-mediated post-translational modifications. Here, we demonstrate that SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on lysine 65 residue, which efficiently mediates SARS2-NP’s ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS). Thereby innate antiviral immune response suppressed robustly. These roles can be achieved through intermolecular association between SUMO conjugation a newly identified SUMO-interacting motif SARS2-NP. Importantly, widespread SARS2-NP R203K mutation gains novel site SUMOylation further increases LLPS immunosuppression. Notably, E3 ligase TRIM28 responsible for catalyzing SUMOylation. An interfering peptide targeting interaction was screened out block LLPS, consequently inhibit replication rescue immunity. Collectively, these data critical virulence, therefore provide strategy antagonize SARS-CoV-2.

Language: Английский

Citations

21
Genomic Perspectives on the Emerging SARS-CoV-2 Omicron Variant DOI Creative Commons
Wentai Ma, Jing Yang, Haoyi Fu

et al.

Genomics Proteomics & Bioinformatics, Journal Year: 2022, Volume and Issue: 20(1), P. 60 - 69

Published: Jan. 13, 2022

Abstract A new variant of concern for SARS-CoV-2, Omicron (B.1.1.529), was designated by the World Health Organization on November 26, 2021. This study analyzed viral genome sequencing data 108 samples collected from patients infected with Omicron. First, we found that enrichment efficiency nucleic acids reduced due to mutations in region where primers anneal to. Second, possesses an excessive number compared other variants circulating at same time (median: 62 vs. 45), especially Spike gene. Mutations gene confer alterations 32 amino acid residues, more than those observed SARS-CoV-2 variants. Moreover, a large nonsynonymous occur codons residues located surface protein, which could potentially affect replication, infectivity, and antigenicity SARS-CoV-2. Third, there are 53 between its closest sequences available public databases. Many these were rarely databases had low mutation rate. In addition, linkage disequilibrium low, limited concurrently genome, suggesting would be different evolutionary branch currently prevalent To improve our ability detect track source rapidly, it is imperative further strengthen genomic surveillance sharing globally timely manner.

Language: Английский

Citations

67
Clinical Severity of SARS-CoV-2 Omicron Variant Compared with Delta among Hospitalized COVID-19 Patients in Belgium during Autumn and Winter Season 2021–2022 DOI Creative Commons
Nina Van Goethem, Pui Yan Jenny Chung, Marjan Meurisse

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(6), P. 1297 - 1297

Published: June 14, 2022

This retrospective multi-center matched cohort study assessed the risk for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality in hospitalized patients when infected with Omicron variant compared to Delta variant. The is based on a causal framework using individually-linked data from national registries. population consisted 954 (of which, 445 were Omicron) above 18 years old admitted Belgian hospital during autumn winter season 2021–2022, available viral genomic data. Patients hospital, whereas other possible confounders (demographics, comorbidities, vaccination status, socio-economic ICU occupancy) adjusted by multivariable logistic regression analysis. estimated standardized admission was significantly lower (RR = 0.63; 95% CI (0.30; 0.97) RR 0.56; (0.14; 0.99), respectively) variant, not different according SARS-CoV-2 0.78, (0.28–1.29)). demonstrates added value integrated clinical surveillance recognize multifactorial nature pathogenesis.

Language: Английский

Citations

64
Mutations in SARS-CoV-2 structural proteins: a global analysis DOI Creative Commons
Mohammad Abavisani, Karim Rahimian, Bahar Mahdavi

et al.

Virology Journal, Journal Year: 2022, Volume and Issue: 19(1)

Published: Dec. 18, 2022

Abstract Background Emergence of new variants mainly concerns (VOC) is caused by mutations in main structural proteins severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we aimed to investigate the among SARS-CoV-2 globally. Methods We analyzed samples amino-acid sequences (AASs) for envelope (E), membrane (M), nucleocapsid (N), and spike (S) from declaration 2019 (COVID-19) as pandemic January 2022. The presence location were then investigated aligning reference sequence categorizing them based on frequency continent. Finally, related human genes with viral discovered, their interactions reported. Results results indicated that most relative E, M, N, S AASs occurred regions 7 14, 66 88, 164 205, 508 635 AAs, respectively. frequent T9I, I82T, R203M/R203K, D614G. D614G was mutation all six geographical areas. Following D614G, L18F, A222V, E484K, N501Y, respectively, ranked protein Besides, A-kinase Anchoring Protein 8 Like (AKAP8L) shown linkage unit between E cluster genes. Conclusion Screening can help scientists introduce better drug vaccine development strategies.

Language: Английский

Citations

59
Phase separation in viral infections DOI
Haohua Li, Christina Ernst, Marta Kolonko

et al.

Trends in Microbiology, Journal Year: 2022, Volume and Issue: 30(12), P. 1217 - 1231

Published: July 25, 2022

Language: Английский

Citations

57
Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein DOI Creative Commons
Huaying Zhao,

Ai Nguyen,

Di Wu

et al.

PNAS Nexus, Journal Year: 2022, Volume and Issue: 1(2)

Published: May 1, 2022

Abstract Worldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well characteristic other viral proteins. Besides their epidemiological importance, the observed sequences present an ensemble of viable protein variants, and thereby a source information on structure function. Charting mutational landscape nucleocapsid (N) that facilitates assembly, we observe variability exceeding with more than 86% residues can be substituted, average by three to four different amino acids. However, exhibit uneven distribution tracks known structural features but also reveals highly protected stretches unknown One these conserved regions is central disordered linker proximal N-G215C mutation has become dominant Delta variant, outcompeting G215 variants without further or N-protein substitutions. Structural models suggest G215C stabilizes transient helices serving protein–protein interaction interfaces. Comparing variant ancestral version biophysical experiments, find significantly compact less structure. exhibits substantially stronger self-association, shifting unliganded from dimeric tetrameric oligomeric state, which leads enhanced coassembly nucleic This suggests sequence mirrored high plasticity properties, hypothesize exploited achieve greater efficiency infectivity.

Language: Английский

Citations

56
Understanding the omicron variant (B.1.1.529) of SARS-CoV-2: Mutational impacts, concerns, and the possible solutions DOI Open Access
Fahadul Islam, Manish Dhawan, Mohamed H. Nafady

et al.

Annals of Medicine and Surgery, Journal Year: 2022, Volume and Issue: 78

Published: May 7, 2022

Despite many nations' best efforts to contain the so-called COVID-19 pandemic, emergence of SARS-CoV-2 Omicron strain (B.1.1.529) has been identified as a serious concern. After more than two years pandemic and year worldwide vaccination efforts, globe will not be free variants such Delta variants. According current statistics, variant 30 mutations when contrasted other VOCs Alpha (B.1.1.7), Beta (B.1.351), (B.1.617.2). High numbers changes, particularly in spike protein (S-Protein), raise worries about virus's capacity resist pre-existing immunity acquired by or spontaneous infection antibody-based therapy. The raised international concerns, resuming travel bans coming up with questions its severity, transmissibility, testing, detection, vaccines efficiency against it. Additionally, inadequate health care infrastructures immunocompromised individuals increase susceptibility. status low rates play significant role omicron spreading create fertile ground for producing new As result, this article emphasizes mutational changes their consequences. In addition, potential preventing measures have examined detail.

Language: Английский

Citations

47
A conserved oligomerization domain in the disordered linker of coronavirus nucleocapsid proteins DOI Creative Commons
Huaying Zhao, Di Wu, Sergio A. Hassan

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(14)

Published: April 5, 2023

The nucleocapsid (N-)protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a key role in viral assembly and scaffolding the RNA. It promotes liquid-liquid phase separation (LLPS), forming dense droplets that support ribonucleoprotein particles with as-of-yet unknown macromolecular architecture. Combining biophysical experiments, molecular dynamics simulations, analysis mutational landscape, we describe heretofore oligomerization site contributes to LLPS, is required for higher-order protein-nucleic acid complexes, coupled large-scale conformational changes N-protein upon nucleic binding. self-association interface located leucine-rich sequence intrinsically disordered linker between folded domains formed by transient helices assembling into trimeric coiled-coils. Critical residues stabilizing hydrophobic electrostatic interactions adjacent are highly protected against mutations viable SARS-CoV-2 genomes, motif conserved across related coronaviruses, thus presenting target antiviral therapeutics.

Language: Английский

Citations

32