Inhibition of Protein
            <i>N-</i>
            Glycosylation Blocks SARS-CoV-2 Infection

Casas-Sánchez, Aitor; Romero-Ramirez, Alessandra; Hargreaves, E. R.; Ellis, Cameron; Grajeda, Brian; Estevao, Igor L.; Patterson, Edward I; Hughes, Grant L.; Almeida, Igor C.; Zech, Tobias; Acosta-Serrano, Álvaro

doi:10.1128/mbio.03718-21

Cited by 28 publications

(35 citation statements)

References 51 publications

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“…Glycosylation mediates interactions with the calnexin/calreticulin folding pathway and secretion checkpoint. Inhibitors targeting entry into the pathway, for example, inhibition of α-glucosidases by iminosugar-containing/based compounds, such as N -butyldeoxynojirimycin (NB-DNJ) and N -butyldeoxygalactonojirimicin (NB-DGJ), have led to a marked reduction in viral infectivity [ 40 ]. Beyond the capacity for glycans to mediate chaperone interactions, they can also impart physicochemical stability.…”

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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“…Viral evolution and mutation can alter the glycoproteome profile which contributes to the survival and transmissibility of the viruses (H. C. Huang et al, 2021 ; Zhao et al, 2020 ). For example, the glycosylated S‐protein of SARS‐CoV‐2 improves viral entry and binding efficacy with the host receptors that when inhibited has shown a reduction in the spread of the infection (Casas‐Sanchez et al, 2022 ; Yang, Hughes, et al, 2020 ). Understanding the glycoproteome alterations are also essential in identifying vaccine targets, particularly of the receptor binding domain (RBD) of the S‐protein (Gstöttner et al, 2021 ; Watanabe, Berndsen, et al, 2020 ; Yang, Hughes, et al, 2020 ).…”

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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“…Miglustat showed overall reduction in infection in these cells, reduced cluster of infected cells, protected against cytopathic effects, and moderately reduced viral titer in supernatant. 31 Miglustat was also found to be effective against SARS-CoV-2 with an IC 50 value of 41 ± 22 μM in a plaque reduction assay on Vero E6 cells. 1 …”

Section: Potential Glycosylation Inhibitors For Sars-cov-2mentioning

confidence: 96%

Exploring the Potential of Chemical Inhibitors for Targeting Post-translational Glycosylation of Coronavirus (SARS-CoV-2)

et al. 2022

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The Spike (S) protein of SARS-CoV-2 expressed on the viral cell surface is of particular importance as it facilitates viral entry into the host cells. The S protein is heavily glycosylated with 22 N-glycosylation sites and a few N-glycosylation sites. During the viral surface protein synthesis via the host ribosomal machinery, glycosylation is an essential step in post-translational modifications (PTMs) and consequently vital for its life cycle, structure, immune evasion, and cell infection. Interestingly, the S protein of SARS-CoV-2 and the host receptor protein, ACE2, are also extensively glycosylated and these surface glycans are critical for the viral–host cell interaction for viral entry. The glycosylation pathway of both virus (hijacked from the host biosynthetic machinery) and target cells crucially affect SARS-CoV-2 infection at different levels. For example, the glycosaminoglycans (GAGs) of host cells serve as a cofactor as they interact with the receptor-binding domain (RBD) of S-glycoprotein and play a protective role in host immune evasion via masking the viral peptide epitopes. Hence, the post-translational glycan biosynthesis, processing, and transport events could be potential targets for developing therapeutic drugs and vaccines. Especially, inhibition of the N-glycan biosynthesis pathway amplifies S protein proteolysis and, thus, blocks viral entry. The chemical inhibitors of SARS-CoV-2 glycosylation could be evaluated for Covid-19. In this review, we discuss the current status of the chemical inhibitors (both natural and synthetically designed inhibitors) of viral glycosylation for Covid-19 and provide a future perspective. It could be an important strategy in targeting the various emerging SARS-CoV-2 variants of concern (VOCs), as these inhibitors are postulated to aid in reducing the viral load as well as infectivity.

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Inhibition of Protein N- Glycosylation Blocks SARS-CoV-2 Infection

Abstract: The coronavirus SARS-CoV-2 uses its spike surface proteins to infect human cells. Spike proteins are heavily modified with several N -glycans, which are predicted to modulate their function.

Cited by 28 publications

References 51 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

Exploring the Potential of Chemical Inhibitors for Targeting Post-translational Glycosylation of Coronavirus (SARS-CoV-2)

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