Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection DOI Creative Commons
Jiakai Hou, Yanjun Wei, Jing Zou

et al.

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

Published: Jan. 2, 2024

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses multi-omics data screen, association studies, single-cell RNA-Seq, host-virus proteins or protein/RNA interactome. This study uncovers many that currently underappreciated, including components V-ATPases, ESCRT, N-glycosylation pathways modulate viral entry and/or replication. The cohesin complex is also identified as an pathway, suggesting important role three-dimensional chromatin organization mediating host-viral interaction. Furthermore, discover another regulator KLF5, transcriptional factor involved sphingolipid metabolism, which up-regulated, harbors genetic variations linked COVID-19 patients with severe symptoms. Anti-viral effects three candidates (DAZAP2/VTA1/KLF5) confirmed individually. Molecular characterization DAZAP2/VTA1/KLF5-knockout cells highlights involvement genes related coagulation system determining severity COVID-19. Together, our results provide further resources understanding network during may help develop new countermeasure strategies.

Language: Английский

COVID-19 in pregnancy: implications for fetal brain development DOI Creative Commons
Lydia L. Shook, Elinor L. Sullivan, Jamie O. Lo

et al.

Trends in Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 319 - 330

Published: Feb. 14, 2022

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has rarely observed SARS-CoV-2 to date, given potential for profound maternal immune activation (MIA), likely. Here we review evidence that and other viral can result maternal, placental, activation, ultimately offspring morbidity. Finally, highlight need cellular models development better understand short- long-term impacts next generation.

Language: Английский

Citations

118
Neutralization, effector function and immune imprinting of Omicron variants DOI Creative Commons
Amin Addetia, Luca Piccoli, James Brett Case

et al.

Nature, Journal Year: 2023, Volume and Issue: 621(7979), P. 592 - 601

Published: Aug. 30, 2023

Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding region S309 antibody (the parent for sotrovimab) human explain preservation binding through conformational selection, altered recognition immune evasion. We show sotrovimab binds avidly all variants, promotes Fc-dependent effector functions protects mice challenged hamsters XBB.1.5. Vaccine-elicited plasma antibodies cross-react trigger against current despite a reduced neutralizing activity, suggesting mechanism protection disease, exemplified by S309. Cross-reactive RBD-directed memory B cells remained dominant even after two exposures spikes, underscoring role persistent imprinting.

Language: Английский

Citations

117
Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants DOI Creative Commons
James W. Saville, Dhiraj Mannar, Xing Zhu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 8, 2022

The Delta and Kappa variants of SARS-CoV-2 co-emerged in India late 2020, with the variant underlying resurgence COVID-19, even countries high vaccination rates. In this study, we assess structural biochemical aspects viral fitness for these two using cryo-electron microscopy (cryo-EM), ACE2-binding antibody neutralization analyses. Both demonstrate escape antibodies targeting N-terminal domain, an important immune hotspot neutralizing epitopes. Compared to wild-type lineages, spike proteins show modest increase ACE2 affinity, likely due enhanced electrostatic complementarity at RBD-ACE2 interface, which characterize by cryo-EM. Unexpectedly, trimers form a head-to-head dimer-of-trimers assembly, is result E484Q mutation unknown biological implications. combination increased binding provides explanation, part, rapid global dominance variant.

Language: Английский

Citations

96
Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2 DOI Creative Commons
Kathryn E. Kistler, John Huddleston, Trevor Bedford

et al.

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(4), P. 545 - 555.e4

Published: March 22, 2022

The SARS-CoV-2 pandemic has resulted in numerous virus variants, some of which have altered receptor-binding or antigenic phenotypes. Here, we quantify the degree to adaptive evolution is driving accumulation mutations across genome. We correlate clade growth with mutation accumulation, compare rates nonsynonymous synonymous divergence, assess temporal clustering mutations, and evaluate evolutionary success individual mutations. find that spike S1 focus but also identify positively selected other proteins (notably Nsp6) are sculpting trajectory SARS-CoV-2. Adaptive changes accumulated rapidly, resulting a remarkably high ratio divergence 2.5× greater than observed influenza hemagglutinin HA1 at beginning 2009 H1N1 pandemic. These findings uncover adaptation suggest might undergo drift.

Language: Английский

Citations

92
SARS-CoV-2: Evolution and Emergence of New Viral Variants DOI Creative Commons
Verónica Roxana Flores-Vega,

Jessica Viridiana Monroy-Molina,

Luis Enrique Jiménez-Hernández

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(4), P. 653 - 653

Published: March 22, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for disease 2019 (COVID-19). high rate of mutation this virus associated with a quick emergence new viral variants that have been rapidly spreading worldwide. Several mutations documented in receptor-binding domain (RBD) spike protein increases interaction between SARS-CoV-2 and its cellular receptor, angiotensin-converting enzyme (ACE2). Mutations can increase spread rate, severity, ability to evade either immune protective responses, monoclonal antibody treatments, or efficacy current licensed vaccines. This review aimed highlight functional classification used by World Health Organization (WHO), Phylogenetic Assignment Named Global Outbreak (PANGO), Initiative on Sharing All Influenza Data (GISAID), Nextstrain, an open-source project harness scientific public health potential pathogen genome data, chronological concern (VOCs) interest (VOIs), major findings related spread, are involved evasion host responses elicited prior infections protection induced vaccination.

Language: Английский

Citations

89
Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways DOI Creative Commons
Naoko Iwata‐Yoshikawa, Masatoshi Kakizaki,

Nozomi Shiwa-Sudo

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 15, 2022

Abstract In cultured cells, SARS-CoV-2 infects cells via multiple pathways using different host proteases. Recent studies have shown that the furin and TMPRSS2 (furin/TMPRSS2)-dependent pathway plays a minor role in infection of Omicron variant. Here, we confirm uses furin/TMPRSS2-dependent inefficiently enters mainly cathepsin-dependent endocytosis TMPRSS2-expressing VeroE6/TMPRSS2 Calu-3 cells. This is case despite efficient cleavage spike protein Omicron. However, airways TMPRSS2-knockout mice, significantly reduced. We furthermore show propagation mouse-adapted QHmusX strain human clinical isolates Beta Gamma reduced mice. Therefore, variant isn’t an exception vivo, analysis with mice important when evaluating variants. conclusion, this study shows critically for murine airways, including

Language: Английский

Citations

83
The Remarkable Evolutionary Plasticity of Coronaviruses by Mutation and Recombination: Insights for the COVID-19 Pandemic and the Future Evolutionary Paths of SARS-CoV-2 DOI Creative Commons
Grigoris D. Amoutzias, Marios Nikolaidis, Eleni Tryfonopoulou

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(1), P. 78 - 78

Published: Jan. 2, 2022

Coronaviruses (CoVs) constitute a large and diverse subfamily of positive-sense single-stranded RNA viruses. They are found in many mammals birds have great importance for the health humans farm animals. The current SARS-CoV-2 pandemic, as well previous epidemics that were zoonotic origin, highlights studying evolution entire CoV order to understand how novel strains emerge which molecular processes affect their adaptation, transmissibility, host/tissue tropism, patho non-homologous genicity. In this review, we focus on studies over last two years reveal impact point mutations, insertions/deletions, intratypic/intertypic homologous recombination events CoVs. We discuss whether next generations vaccines should be directed against other proteins addition or instead spike. Based observed patterns subfamily, five scenarios future evolutionary path COVID-19 pandemic. Finally, within context, recently emerged Omicron (B.1.1.529) VoC.

Language: Английский

Citations

82
The Delta and Omicron Variants of SARS-CoV-2: What We Know So Far DOI Creative Commons
Vivek P. Chavda, Rajashri Bezbaruah,

Kangkan Deka

et al.

Vaccines, Journal Year: 2022, Volume and Issue: 10(11), P. 1926 - 1926

Published: Nov. 14, 2022

The world has not yet completely overcome the fear of havoc brought by SARS-CoV-2. virus undergone several mutations since its initial appearance in China December 2019. Several variations (i.e., B.1.616.1 (Kappa variant), B.1.617.2 (Delta B.1.617.3, and BA.2.75 (Omicron variant)) have emerged throughout pandemic, altering virus's capacity to spread, risk profile, even symptoms. Humanity faces a serious threat as long keeps adapting changing fundamental function evade immune system. Delta variant two escape alterations, E484Q L452R, well other mutations; most notable these is P681R, which expected boost infectivity, whereas Omicron about 60 with certain deletions insertions. 40-60% more contagious comparison Alpha variant. Additionally, AY.1 lineage, also known "Delta plus" variant, surfaced result mutation was one causes life-threatening second wave coronavirus disease 2019 (COVID-19). Nevertheless, recent variants represent reminder that COVID-19 epidemic far from ending. sparked fervor investigation on why initially appeared propagate so much rapidly than three concerns (VOCs), whether it threatening those ways, how type mutations, induce minor changes proteins, can wreck trouble. This review sheds light pathogenicity, treatments, impact vaccine efficacy

Language: Английский

Citations

75
SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity DOI Creative Commons
Haolin Liu, Pengcheng Wei, John W. Kappler

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 27, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has lasted more than years with over 260 million infections and 5 deaths worldwide as of November 2021. To combat the virus, monoclonal antibodies blocking virus binding to human receptor, angiotensin converting enzyme (ACE2), have been approved treat infected patients. Inactivated whole or full-length spike encoding adenovirus mRNA vaccines are being used immunize public. However, SARS-CoV-2 variants emerging. These, some extent, escape neutralization by therapeutic vaccine-induced immunity. Thus, breakthrough reported in previously virus-infected fully vaccinated individuals. receptor domain (RBD) protein reacts host ACE2, leading entry into cell. It is also major antigenic site 90% broadly neutralizing from either patients individuals targeting RBD. Therefore, mutations RBD region effective ways for gain infectivity immunity built up original infections. In this review, we focus on impact concern (VOC) interest (VOI) ACE2 affinity serum antibody neutralization. We provide structure models show how VOC VOI affect allow antibody, bamlanivimab.

Language: Английский

Citations

72
An early warning system for emerging SARS-CoV-2 variants DOI Open Access
Lorenzo Subissi, Anne von Gottberg, Lipi Thukral

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(6), P. 1110 - 1115

Published: May 30, 2022

Language: Английский

Citations

72