Systematic Exploration of SARS-CoV-2 Adaptation to Vero E6, Vero E6/TMPRSS2, and Calu-3 Cells DOI Creative Commons
Pakorn Aiewsakun, Worakorn Phumiphanjarphak, Natali Ludowyke

et al.

Genome Biology and Evolution, Journal Year: 2023, Volume and Issue: 15(4)

Published: Feb. 28, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, and scientists around the world are currently studying virus intensively in order fight against on-going pandemic of virus. To do so, SARS-CoV-2 is typically grown lab generate viral stocks for various kinds experimental investigations. However, accumulating evidence suggests that such viruses often undergo cell culture adaptation. Here, we systematically explored adaptation two variants, namely B.1.36.16 variant AY.30 variant, a sub lineage B.1.617.2 (Delta) propagated three different lines, including Vero E6, E6/TMPRSS2, Calu-3 cells. Our analyses detected numerous potential changes scattering across entire genome, many which could be found naturally circulating isolates. Notable ones included mutations spike glycoprotein's multibasic cleavage site, Omicron-defining H655Y mutation on glycoprotein, as well nucleocapsid protein's linker region, all were E6-specific. also identified deletion non-structural protein 1 membrane glycoprotein Calu-3-specific changes. S848C 3, located papain-like protease domain, was change, lines. results highlight high adaptability, emphasize need deep-sequence cultured samples when used intricate sensitive biological experiments, illustrate power evolutionary study shedding lights landscape.

Language: Английский

Mechanisms of SARS-CoV-2 entry into cells DOI Creative Commons
Cody B. Jackson, Michael Farzan, Bing Chen

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 3 - 20

Published: Oct. 5, 2021

Language: Английский

Citations

2502
SARS-CoV-2 pathogenesis DOI Open Access
Mart M. Lamers, Bart L. Haagmans

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(5), P. 270 - 284

Published: March 30, 2022

Language: Английский

Citations

702
Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron DOI Open Access
Huiping Shuai, Jasper Fuk‐Woo Chan, Bingjie Hu

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 693 - 699

Published: Jan. 21, 2022

Language: Английский

Citations

618
The next phase of SARS-CoV-2 surveillance: real-time molecular epidemiology DOI Creative Commons
Bas B. Oude Munnink, Nathalie Worp, David F. Nieuwenhuijse

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(9), P. 1518 - 1524

Published: Sept. 1, 2021

Language: Английский

Citations

221
Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission DOI Creative Commons
Alba Escalera, Ana S. González-Reiche, Sadaf Aslam

et al.

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(3), P. 373 - 387.e7

Published: Jan. 21, 2022

Language: Английский

Citations

176
Proteolytic activation of SARS‐CoV‐2 spike protein DOI Creative Commons
Makoto Takeda

Microbiology and Immunology, Journal Year: 2021, Volume and Issue: 66(1), P. 15 - 23

Published: Sept. 25, 2021

Spike (S) protein cleavage is a crucial step in coronavirus infection. In this review, process discussed, with particular focus on the novel coronavirus, severe acute respiratory syndrome 2 (SARS-CoV-2). Compared influenza virus and paramyxovirus membrane fusion proteins, activation mechanism of S much more complex. The has two sites (S1/S2 S2'), motif for furin protease at S1/S2 site that results from unique four-amino acid insertion one distinguishing features SARS-CoV-2. viral particle incorporates protein, which already undergone by furin, then undergoes further S2' site, mediated type II transmembrane serine (TMPRSS2), after binding to receptor angiotensin-converting enzyme (ACE2) facilitate plasma membrane. addition, SARS-CoV-2 can enter cell endocytosis be proteolytically activated cathepsin L, although not major mode variants enhanced infectivity have been emerging throughout ongoing pandemic, there close relationship between changes cleavability. All four concern carry D614G mutation, indirectly enhances cleavability furin. P681R mutation delta variant directly increases cleavability, enhancing virulence. Changes significantly impact infectivity, tissue tropism, Understanding these mechanisms critical counteracting pandemic.

Language: Английский

Citations

171
The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways DOI Creative Commons
Manon Laporte,

Valerie Raeymaekers,

Ria Van Berwaer

et al.

PLoS Pathogens, Journal Year: 2021, Volume and Issue: 17(4), P. e1009500 - e1009500

Published: April 22, 2021

The high transmissibility of SARS-CoV-2 is related to abundant replication in the upper airways, which not observed for other highly pathogenic coronaviruses SARS-CoV and MERS-CoV. We here reveal features coronavirus spike (S) protein, optimize virus towards human respiratory tract. First, S proteins exhibit an intrinsic temperature preference, corresponding with or lower airways. Pseudoviruses bearing (SARS-2-S) were more infectious when produced at 33°C instead 37°C, a property shared protein HCoV-229E, common cold coronavirus. In contrast, MERS-CoV favored accordance preference Next, SARS-2-S-driven entry was efficiently activated by only TMPRSS2, but also TMPRSS13 protease, thus broadening cell tropism SARS-CoV-2. Both proteases proved relevant context authentic replication. appeared effective activator virulent low HCoV-229E virus. Activation SARS-2-S these surface requires processing S1/S2 cleavage loop, both furin recognition motif extended loop length critical. Conversely, deletion mutants significantly increased cathepsin-rich cells. Finally, we demonstrate that D614G mutation increases stability, particularly and, enhances its use cathepsin L pathway. This indicates link between stability usage this alternative route entry. Since properties may promote spread, they potentially explain why spike-G614 variant has replaced early D614 become globally predominant. Collectively, our findings adaptive mechanisms whereby adjusted match protease conditions enhance transmission pathology.

Language: Английский

Citations

118
SARS-CoV-2 spike engagement of ACE2 primes S2′ site cleavage and fusion initiation DOI Creative Commons
Yu Shi, Xu Zheng, Bingjie Zhou

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 119(1)

Published: Dec. 20, 2021

Significance The SARS-CoV-2 spike protein is responsible for host receptor recognition, membrane fusion, and viral infection. Understanding the cellular inhibiting molecular mechanisms of spike-driven entry a research priority in curbing ongoing pandemic preventing future coronavirus outbreaks. Here, we highlight that generation S2′ fragments, proteolytic event occurring within S2 subunit, switch coupled to fusion. Downstream syncytia formation requires presence an cleavage site at arginine 815 but not 685. Hence, processing upon its engagement ACE2 may serve as potential antiviral target against current related strains.

Language: Английский

Citations

107
A coronavirus assembly inhibitor that targets the viral membrane protein DOI Creative Commons
Manon Laporte, Dirk Jochmans,

Dorothée Bardiot

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

Citations

3
A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses DOI Creative Commons
Joep Beumer, Maarten H. Geurts, Mart M. Lamers

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 17, 2021

Abstract Rapid identification of host genes essential for virus replication may expedite the generation therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells vivo, leading to discoveries not be translated clinic. Intestinal organoids increasingly used model human disease and amenable genetic engineering. To discern which factors reliable anti-coronavirus targets, we generate mutant clonal IOs 19 previously implicated coronavirus biology. We verify ACE2 DPP4 as entry receptors SARS-CoV/SARS-CoV-2 MERS-CoV respectively. SARS-CoV-2 does require endosomal Cathepsin B/L proteases, but specifically depends on surface protease TMPRSS2. Other TMPRSS family members were essential. The newly emerging variant B.1.1.7, well SARS-CoV similarly depended These findings underscore relevance non-transformed models research, identify TMPRSS2 an attractive pan-coronavirus target, demonstrate organoid knockout biobank is a valuable tool investigate biology current future coronaviruses.

Language: Английский

Citations

74