The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint

Guo, Hua; Li, Ang; Lin, Haofeng; Liu, Meiqin; Chen, Jing; Li, Bei; Wang, Yi; Letko, Michael; Peng, Wenjie; Z, Shi

doi:10.1128/jvi.00958-22

Cited by 11 publications

(17 citation statements)

References 68 publications

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“…Binding between proteins and cells was detected by a Dylight 650 labeled goat anti-human IgG Fc antibody (Abcam, ab98622). For pseudotyped particles binding assay, the pseudotypes were generated as described above and purified through ultracentrifugation as previously described ( 57 ). The purified pseudotyped particles were incubated with Huh-7 cells at 4°C for 1 h before fixation by 4% PFA and permeabilization by PBS plus 0.25% Triton X-100.…”

Section: Methodsmentioning

confidence: 99%

ACE2-Independent Bat Sarbecovirus Entry and Replication in Human and Bat Cells

Guo

Dong

et al. 2022

mBio

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Our studies demonstrate that some unexplored sarbecoviruses are capable of replicating in human and bat cells in an ACE2-independent way but need a high trypsin environment. We found that trypsin is not compensated by other known proteases involved in some coronavirus entry. This work provides important information that the trypsin-dependent entry may be a widely employed mechanism for coronaviruses and will help for further understanding the biological features of the less-studied viruses.

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Section: Methodsmentioning

confidence: 99%

ACE2-Independent Bat Sarbecovirus Entry and Replication in Human and Bat Cells

Guo

Dong

et al. 2022

mBio

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“…51 Glycosylations act as shields against the host immune response, as mutations in glycosites can alter antibody susceptibility by sterically hindering access to antibody binding sites. 16,38 Structure-guided glycosome studies can provide insights into antibody evasion or evolutionary history. For example, NTD glycosite N96 and RBD glycosite N344 are conserved in all three SARSr-CoVs, but are not observed in SARS-CoV-2 (7E7B), suggesting that the civet and bat SARSr-CoVs may be more resistant to antibodies that recognize this region.…”

Section: Discussionmentioning

confidence: 99%

“…In all these glycoproteins N2, N3 and N5 loops are shorter than in RaTG13, consistent with research showing large variations in NTD length across the sarbecovirus family, indicating frequent loop remodeling. [36][37][38][39][40][41][42]…”

Section: Structural Conservation Amongst Sarsr-cov Glycoproteinsmentioning

confidence: 99%

Cryo-EM reveals variation in structural motifs within animal SARS-related coronavirus spike proteins

Bostina

Hills

Eruera

et al. 2023

Preprint

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SARS-CoV-2 is the third known coronavirus (CoV) that has crossed the animal-human barrier in the last two decades. However, little structural information exists related to the close genetic species within the SARS-related coronaviruses. Here, we present three novel SARS-related CoV spike protein structures solved by single particle cryo-electron microscopy analysis derived from bat (SL-CoV WIV1) and civet (CoV-SZ3, CoV-007) hosts. We report complex glycan trees that decorate the glycoproteins and density for water molecules which facilitated modeling of the water molecule coordination networks within structurally important regions. We note structural conservation of the fatty acid binding pocket and presence of a linoleic acid molecule, which are associated with stabilization of the receptor binding domains in the “down” conformation. Additionally, the N-terminal biliverdin binding pocket is occupied by a density in all the structures. Finally, we analyzed structural differences in a loop of the receptor binding motif between coronaviruses known to infect humans and the animal coronaviruses described in this study, which regulate binding to the human angiotensin converting enzyme 2 receptor. This study offers a structural framework to evaluate the origins of SARS-CoV-2, the risk of future cross-species transmission, the ability to inform pandemic prevention, and aid in the development of pan-neutralizing treatments.

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“…A characterization of glycan binding capability of spike‐NTD from betacoronaviruses of non‐human hosts revealed that the spike‐NTDs engaged uncharacterized glycan‐conjugated molecules in vitro and depletion of sialic acids from host cells enhanced viral entry, suggesting that SARS‐related coronaviruses retained glycan‐binding in their NTDs. However, such interaction did not contribute to viral entry 89 . Understanding glycobiology in non‐human hosts and the biology of SARS‐related viruses will shed light on the function of these conserved galectin‐like NTDs in defining host tropism, cross‐species transmission and viral infectivity.…”

Section: Future Challenges and Conclusionmentioning

confidence: 99%

“…However, such interaction did not contribute to viral entry. 89 Understanding glycobiology in non‐human hosts and the biology of SARS‐related viruses will shed light on the function of these conserved galectin‐like NTDs in defining host tropism, cross‐species transmission and viral infectivity. It will aid early detection and prevention of spill events that may cause future pandemics.…”

Section: Future Challenges and Conclusionmentioning

confidence: 99%

Involvement of sialoglycans in SARS‐COV‐2 infection: Opportunities and challenges for glyco‐based inhibitors

Kuhaudomlarp

2022

IUBMB Life

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Viral infections have been the causes of global pandemics, including the ongoing coronavirus disease 2019, which prompted the investigation into the infection mechanisms to find treatment and aid the vaccine design. Betacoronaviruses use spike glycoprotein on their surface to bind to host receptors, aiding their host attachment and cell fusion. Protein-glycan interaction has been implicated in the viral entry mechanism of many viruses and has recently been shown in SARS-CoV-2. Here, we reviewed the current knowledge on protein-glycan interactions that facilitate SARS-CoV-2 host entry, with special interest in sialoglycans present on both the virions and host cell surfaces. We also analyze how such information provides opportunities and challenges in glyco-based inhibitors.

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The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint

Cited by 11 publications

References 68 publications

ACE2-Independent Bat Sarbecovirus Entry and Replication in Human and Bat Cells

ACE2-Independent Bat Sarbecovirus Entry and Replication in Human and Bat Cells

Cryo-EM reveals variation in structural motifs within animal SARS-related coronavirus spike proteins

Involvement of sialoglycans in SARS‐COV‐2 infection: Opportunities and challenges for glyco‐based inhibitors

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