Principles of SARS-CoV-2 glycosylation

Chawla, Himanshi; Fadda, Elisa; Crispin, Max

doi:10.1016/j.sbi.2022.102402

Cited by 39 publications

(42 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The N-linked glycans of SARS-CoV-2 S protein are essential for the structure and function of the protein. The glycans are fundamental for the correct folding of the protein, shield the epitopes from the antibody recognition and modulate the structure and dynamics of the S protein [ 30 ]. MD simulations [ 25 , 31 , 32 ], and experimental data [ 31 ] show that the glycans linked to asparagine residues 165, 234 and 343 deeply influence the dynamics of the opening of S protein with a profound effect on the biological role of this protein on the viral infection.…”

Section: Resultsmentioning

confidence: 99%

Structural Evolution of Delta (B.1.617.2) and Omicron (BA.1) Spike Glycoproteins

Prandi

Mavian

Giombini

et al. 2022

IJMS

View full text Add to dashboard Cite

The vast amount of epidemiologic and genomic data that were gathered as a global response to the COVID-19 pandemic that was caused by SARS-CoV-2 offer a unique opportunity to shed light on the structural evolution of coronaviruses and in particular on the spike (S) glycoprotein, which mediates virus entry into the host cell by binding to the human ACE2 receptor. Herein, we carry out an investigation into the dynamic properties of the S glycoprotein, focusing on the much more transmissible Delta and Omicron variants. Notwithstanding the great number of mutations that have accumulated, particularly in the Omicron S glycoprotein, our data clearly showed the conservation of some structural and dynamic elements, such as the global motion of the receptor binding domain (RBD). However, our studies also revealed structural and dynamic alterations that were concentrated in the aa 627–635 region, on a small region of the receptor binding motif (aa 483–485), and the so-called “fusion-peptide proximal region”. In particular, these last two S regions are known to be involved in the human receptor ACE2 recognition and membrane fusion. Our structural evidence, therefore, is likely involved in the observed different transmissibility of these S mutants. Finally, we highlighted the role of glycans in the increased RBD flexibility of the monomer in the up conformation of Omicron.

show abstract

Section: Resultsmentioning

confidence: 99%

Structural Evolution of Delta (B.1.617.2) and Omicron (BA.1) Spike Glycoproteins

Prandi

Mavian

Giombini

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Each monomer in the S protein trimer has 22 glycosylation sites (shown in Figure 1A ) ( 8 , 16 , 17 ). Glycosylation is important in protein conformation, target binding, and host evasion ( 7 , 8 , 18 ). The soluble carbohydrate pattern recognition receptors of the innate immune system could hinder ACE2 - S protein ligation through several different pathways including potential direct competition, inducing conformational changes that prevent receptor recognition, or sequestering the virus through opsonization for clearance by macrophages ( 19 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

SP-A binding to the SARS-CoV-2 spike protein using hybrid quantum and classical in silico modeling and molecular pruning by Quantum Approximate Optimization Algorithm (QAOA) Based MaxCut with ZDOCK

et al. 2022

View full text Add to dashboard Cite

The pulmonary surfactant protein A (SP-A) is a constitutively expressed immune-protective collagenous lectin (collectin) in the lung. It binds to the cell membrane of immune cells and opsonizes infectious agents such as bacteria, fungi, and viruses through glycoprotein binding. SARS-CoV-2 enters airway epithelial cells by ligating the Angiotensin Converting Enzyme 2 (ACE2) receptor on the cell surface using its Spike glycoprotein (S protein). We hypothesized that SP-A binds to the SARS-CoV-2 S protein and this binding interferes with ACE2 ligation. To study this hypothesis, we used a hybrid quantum and classical in silico modeling technique that utilized protein graph pruning. This graph pruning technique determines the best binding sites between amino acid chains by utilizing the Quantum Approximate Optimization Algorithm (QAOA)-based MaxCut (QAOA-MaxCut) program on a Near Intermediate Scale Quantum (NISQ) device. In this, the angles between every neighboring three atoms were Fourier-transformed into microwave frequencies and sent to a quantum chip that identified the chemically irrelevant atoms to eliminate based on their chemical topology. We confirmed that the remaining residues contained all the potential binding sites in the molecules by the Universal Protein Resource (UniProt) database. QAOA-MaxCut was compared with GROMACS with T-REMD using AMBER, OPLS, and CHARMM force fields to determine the differences in preparing a protein structure docking, as well as with Goemans-Williamson, the best classical algorithm for MaxCut. The relative binding affinity of potential interactions between the pruned protein chain residues of SP-A and SARS-CoV-2 S proteins was assessed by the ZDOCK program. Our data indicate that SP-A could ligate the S protein with a similar affinity to the ACE2-Spike binding. Interestingly, however, the results suggest that the most tightly-bound SP-A binding site is localized to the S2 chain, in the fusion region of the SARS-CoV-2 S protein, that is responsible for cell entry Based on these findings we speculate that SP-A may not directly compete with ACE2 for the binding site on the S protein, but interferes with viral entry to the cell by hindering necessary conformational changes or the fusion process.

show abstract

“…An abundance of under processed oligomannose-type glycans can arise if access to the glycan substrate by ER and cis-Golgi α-mannosidase is impeded, either through protein-glycan or glycan-glycan clashes [53]. This glycan processing prohibition signature is a reliable marker of native-like protein folding [54,55]. Most sites across the SARS-CoV-2 S protein, however, do present a large abundance of fully processed complex-type glycans [39,41,56,57] .…”

Section: Introductionmentioning

confidence: 99%

Natural variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics

Newby

Fogarty

Allen

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity, whether arisen naturally or through vaccination. Understanding the structure of the viral spike assists in determining the impact of mutations on the antigenic surface. One class of mutation impacts glycosylation attachment sites, which have the capacity to influence the antigenic structure beyond the immediate site of attachment. Here, we compare the glycosylation of a recombinant viral spike mimetic of the P.1 (Gamma) strain, which exhibits two additional N-linked glycan sites compared to the equivalent mimetic of the Wuhan strain. We determine the site-specific glycosylation of these variants and investigate the impact of these glycans by molecular dynamics. The N188 site is shown to exhibit very limited glycan maturation, consistent with limited enzyme accessibility. Structural modeling and molecular dynamics reveal that N188 is located within a cavity by the receptor binding domain, which influences the dynamics of these attachment domains. These observations suggest a mechanism whereby mutations affecting viral glycosylation sites have a structural impact across the antigenic surface.

show abstract

Principles of SARS-CoV-2 glycosylation

Cited by 39 publications

References 83 publications

Structural Evolution of Delta (B.1.617.2) and Omicron (BA.1) Spike Glycoproteins

Structural Evolution of Delta (B.1.617.2) and Omicron (BA.1) Spike Glycoproteins

SP-A binding to the SARS-CoV-2 spike protein using hybrid quantum and classical in silico modeling and molecular pruning by Quantum Approximate Optimization Algorithm (QAOA) Based MaxCut with ZDOCK

Natural variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics

Contact Info

Product

Resources

About