Loss of Spike N370 glycosylation as an important evolutionary event for the enhanced infectivity of SARS-CoV-2

Zhang, Shuyuan; Liang, Qingtai; He, Xinheng; Zhao, Cheng; Ren, Wenlin; Yang, Ziqing; Wang, Ziyi; Ding, Qiang; Deng, Haiteng; Wang, Tong; Zhang, Linqi; Wang, Xinquan

doi:10.1038/s41422-021-00600-y

Cited by 38 publications

(38 citation statements)

References 10 publications

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“…Because of this key functional role, the glycan shield evolved significantly along the phylogeny, and it is continually evolving [ 45 ], with the very recent loss of N370 glycosylation due to T372A mutation in SARS-CoV-2. Through molecular dynamics (MD) simulation, it has been observed that presence of both N234 and N370 results in tying the closed RBDs together, and likely hinders the RBD opening [ 45 , 46 , 47 ]. This possibly explains the absence of N370 glycan site in SARS-CoV-2.…”

Section: Role Of Glycans In Protein Folding and Stabilitymentioning

confidence: 99%

Principles of SARS-CoV-2 glycosylation

Chawla

Fadda

Crispin

2022

Current Opinion in Structural Biology

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Section: Role Of Glycans In Protein Folding and Stabilitymentioning

confidence: 99%

Principles of SARS-CoV-2 glycosylation

Chawla

Fadda

Crispin

2022

Current Opinion in Structural Biology

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“…Previously observed on bat and pangolin‐derived coronavirus S‐protein trimers (S. Zhang et al, 2021 ), the glycosylation site at Asn370 was found to be lost in the S‐protein from SARS‐CoV‐2 because of the threonine‐to‐alanine mutation at that position that may have occurred over the viral evolution process. For this reason, the authors attempted to restore this N ‐glycosite of S‐protein expressing it in different systems, and demonstrated through MS, surface plasmon resonance, and molecular dynamic simulation experiments that the absence of glycosylation on Asn370 facilitated a more efficient binding to the ACE2 receptor thereby providing a higher capacity for infection (S. Zhang, Liang, et al, 2022 ).…”

Section: Glycoproteomics‐based Ms Of Sars‐cov‐2 Viral Proteinsmentioning

confidence: 99%

Proteomics‐based mass spectrometry profiling of SARS‐CoV‐2 infection from human nasopharyngeal samples

Chatterjee

Zaia

2022

Mass Spectrometry Reviews

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the cause of the on‐going global pandemic of coronavirus disease 2019 (COVID‐19) that continues to pose a significant threat to public health worldwide. SARS‐CoV‐2 encodes four structural proteins namely membrane, nucleocapsid, spike, and envelope proteins that play essential roles in viral entry, fusion, and attachment to the host cell. Extensively glycosylated spike protein efficiently binds to the host angiotensin‐converting enzyme 2 initiating viral entry and pathogenesis. Reverse transcriptase polymerase chain reaction on nasopharyngeal swab is the preferred method of sample collection and viral detection because it is a rapid, specific, and high‐throughput technique. Alternate strategies such as proteomics and glycoproteomics‐based mass spectrometry enable a more detailed and holistic view of the viral proteins and host–pathogen interactions and help in detection of potential disease markers. In this review, we highlight the use of mass spectrometry methods to profile the SARS‐CoV‐2 proteome from clinical nasopharyngeal swab samples. We also highlight the necessity for a comprehensive glycoproteomics mapping of SARS‐CoV‐2 from biological complex matrices to identify potential COVID‐19 markers.

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“…Furthermore, we and others recently found that loss of N370 glycosylation is an important evolutionary event that enhanced the infectivity of SARS‐CoV‐2 [ 83 , 84 ]. The N‐glycosylation ‐NXS/T‐ sequon is highly conserved among sarbecoviruses at the N370 site, and the N370‐linked glycans have also been observed in the cryo‐EM structures of RaTG13, PCoV_GD and PCoV_GX S glycoproteins.…”

Section: Structural Insights Into the Evolution Of The Cov ...mentioning

confidence: 99%

“…Conversely, an S372A mutation to disrupt the N370 glycosylation site in RaTG13 pseudovirus resulted in significantly enhanced cell entry capacity compared to wild type. Structural studies further showed that, compared to wild‐type SARS‐CoV‐2 S, loss of N370 glycosylation increased the percentage of ‘open’ form SARS‐CoV‐2 S trimers among all particles from ~ 14% to ~ 42%, which is expected to facilitate binding to ACE2 receptor [ 18 , 83 ] (Fig. 4B ).…”

Section: Structural Insights Into the Evolution Of The Cov ...mentioning

confidence: 99%

The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition

Qiao

Zhang

et al. 2022

FEBS Open Bio

Self Cite

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Highly pathogenic human coronaviruses (CoV) including SARS‐CoV, MERS‐CoV and SARS‐CoV‐2 have emerged over the past two decades, resulting in infectious disease outbreaks that have greatly affected public health. The CoV surface spike (S) glycoprotein mediates receptor binding and membrane fusion for cell entry, playing critical roles in CoV infection and evolution. The S glycoprotein is also the major target molecule for prophylactic and therapeutic interventions, including neutralizing antibodies and vaccines. In this review, we summarize key studies that have revealed the structural basis of S‐mediated cell entry of SARS‐CoV, MERS‐CoV and SARS‐CoV‐2. Additionally, we discuss the evolution of the S glycoprotein to realize cross‐species transmission from the viewpoint of structural biology. Lastly, we describe the recent progress in developing antibodies, nanobodies and peptide inhibitors that target the SARS‐CoV‐2 S glycoprotein for therapeutic purposes.

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Loss of Spike N370 glycosylation as an important evolutionary event for the enhanced infectivity of SARS-CoV-2

Cited by 38 publications

References 10 publications

Principles of SARS-CoV-2 glycosylation

Principles of SARS-CoV-2 glycosylation

Proteomics‐based mass spectrometry profiling of SARS‐CoV‐2 infection from human nasopharyngeal samples

The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition

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