Inclusion of glycopeptides in hydrogen/deuterium exchange mass spectrometry analysis of SARS-CoV-2 spike ectodomain provides in-creased sequence coverage DOI Creative Commons
Christopher A. Haynes, Theodore R. Keppel,

Betlehem Mekonnen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 15, 2023

Hydrogen/deuterium exchange mass spectrometry (HDX-MS) can provide precise analysis of a protein’s conformational dynamics across varied states, such as heat-denatured vs. native protein structures, localizing regions that are specifically affected by conditional changes. Maximizing sequence coverage provides high confidence interest were located HDX-MS, but one challenge for complete is N-glycosylation sites. The deuteration glycopeptides has not always been identified in previous reports HDX-MS analyses, causing significant gaps heavily glycosylated proteins and uncertainty structural many throughout glycoprotein. We report the SARS-CoV-2 spike ectodomain its trimeric pre-fusion form, which 22 predicted sites per monomer, with without heat treatment. calculated their isotopic shifts from deuteration. Inclusion deu-terated increased 76% to 84%, demonstrated had deuterated, improved results re-arrangements. deuterated improves glycoproteins viral surface antigens cellular receptors. Abstract Figure

Language: Английский

The first report of SARS-CoV-2 genome in the groundwater of Tehran, Iran: A call to action for public health DOI
S. Mahdi Hosseinian, Seyed Masoud Hosseini,

Paria Barooni Rashno

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Abstract A pandemic of acute respiratory disease referred to as COVID-19 has been caused by the highly infectious and transmissible Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which threatened human health. Although SARS-CoV-2 RNA found in wastewater from numerous regions different countries due fecal shedding infected individuals, there is still little information available regarding how prevalent it other water matrices especially groundwater, where some areas rely on supply drinking water, irrigation farmlands, purposes. This study attempted assess presence this virus genome groundwater samples Tehran, Iran. These were collected seasonally 12 sites over years period (2021–2023). At first, a adsorption-elution (VIRADEL) concentration procedure was tested utilizing an avian coronavirus (infectious bronchitis virus, IBV) process control followed extraction. Subsequently, quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detect E S genes. As result, detected 1 out 96 with 2/53 × 103 3/16 copies/l for genes, respectively. Furthermore, positive sample subjected semi-nested PCR targeting partial gene, direct sequencing, phylogenetic mutation analysis. BA.1 Omicron only identified variant during study. findings show important water-based epidemiology monitor at community-level subsequent exposure, even when prevalence low.

Language: Английский

Citations

0

Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection DOI Open Access
Pushkala Jayaraman, Madhumitha Rajagopal, Ishan Paranjpe

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 26, 2023

Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term dysfunction. However, peripheral blood molecular signatures AKI from COVID-19 their association dysfunction are yet unexplored.

Language: Английский

Citations

1

Fc-independent SARS-CoV-2 infection-enhancing antibodies decouple N-terminal and receptor-binding domains by cross-linking neighboring spikes DOI Open Access
Floris J. van Eerden, Songling Li, Tina Lusiany

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Abstract Antibody dependent enhancement (ADE) is a serious concern in vaccine development. The canonical ADE pathways are on the fragment crystallizable (Fc) region of antibody. In SARS-CoV-2 several antibodies have been discovered that inflict vitro. These target N-terminal domain (NTD) spike protein. We previously proposed these NTD-targeting infection-enhancing (NIEAs) cross-link neighboring proteins via their NTDs, and this results decoupling between NTD receptor binding (RBD), facilitating “RBD down” to “up” transition. study we present combination molecular dynamics simulations cryogenic electron microscopy data that, together, demonstrate NIEAs indeed able proteins, cross-linking RBD domains. findings provide support for an Fc independent pathway not only relevant but also other viruses which undergo conformational change upon host cell entry.

Language: Английский

Citations

0

Application of HDX–MS for the Structural Characterization of Glycoproteins DOI
Miklós Guttman

Royal Society of Chemistry eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 300 - 314

Published: Oct. 16, 2024

Glycosylation is one of the most common and complex post-translational modifications proteins, rendering many proteins evasive to structural analysis. The intrinsic heterogeneity flexibility pose major challenges for traditional elucidation tools. Hydrogen/deuterium exchange coupled mass spectrometry (HDX–MS) an increasingly widespread tool monitoring protein dynamics, including glycoproteins their interactions in fully glycosylated states. Recent advances have largely alleviated historical applying HDX–MS enable in-depth characterization even pinpoint local effects glycosylation.

Language: Английский

Citations

0

Inclusion of glycopeptides in hydrogen/deuterium exchange mass spectrometry analysis of SARS-CoV-2 spike ectodomain provides in-creased sequence coverage DOI Creative Commons
Christopher A. Haynes, Theodore R. Keppel,

Betlehem Mekonnen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 15, 2023

Hydrogen/deuterium exchange mass spectrometry (HDX-MS) can provide precise analysis of a protein’s conformational dynamics across varied states, such as heat-denatured vs. native protein structures, localizing regions that are specifically affected by conditional changes. Maximizing sequence coverage provides high confidence interest were located HDX-MS, but one challenge for complete is N-glycosylation sites. The deuteration glycopeptides has not always been identified in previous reports HDX-MS analyses, causing significant gaps heavily glycosylated proteins and uncertainty structural many throughout glycoprotein. We report the SARS-CoV-2 spike ectodomain its trimeric pre-fusion form, which 22 predicted sites per monomer, with without heat treatment. calculated their isotopic shifts from deuteration. Inclusion deu-terated increased 76% to 84%, demonstrated had deuterated, improved results re-arrangements. deuterated improves glycoproteins viral surface antigens cellular receptors. Abstract Figure

Language: Английский

Citations

0