Carbohydrate Ligands for COVID-19 Spike Proteins

Lee, Yung-Kuo; Chang, Wen-Chiu; Prakash, Ekambaranellore; Peng, Yu-Ju; Tu, Zhijay; Lin, Chun‐Hung; Hsu, Pang-Hung; Chang, Chuan Fa

doi:10.3390/v14020330

Cited by 10 publications

(10 citation statements)

References 79 publications

(83 reference statements)

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“…Viruses bind to sugar chains on host cell membranes, and mutations in these receptor binding proteins are less frequent 29 . Sugar analogs or receptor sugar analogs that block the host cell sugar chains could potentially be used as drugs capable of overcoming viruses with mutagenic potential in their antigenic sites 30 . In conclusion, the SARS-CoV-2 spike glycoprotein plays a key role in the viral cellular attachment and entry processes.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate prolectin-M, a galectin-3 antagonist, blocks SARS-CoV-2 activity

Sigamani¹,

Chen-Walden²,

Pahan³

et al. 2022

ijhs

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The SARS-COV-2 (severe acute respiratory syndrome coronavirus 2) virus binds to human lectins to gain entry into cells to replicate. Blocking the virus’s entry using a complex polysaccharide component of [a (1-6)- D-mannopyranose termed “ProLectin M” has an effect on viral replication as a therapeutic tool and a safe alternative to existing antiviral therapies. Little is known about how galectin-3 inhibits viral entry into cells and its impact on the course of viral infection. Here, we investigated the effect of these non-cytotoxic polysaccharides on Vero cells infected with SARS-CoV-2 and demonstrated a dose-dependent reduction in viral load over a 48-hour viral incubation period. A pilot clinical study in five patients with laboratory-confirmed COVID-19 disease was treated with an oral formulation of ProLectin M, and all patients achieved complete disease remission with zero hospitalization or need for oxygen support. Moreover, the viral load was significantly lowered within 2 days of drug administration. On the viral envelope, glycans often play a crucial role in enabling pathogen transmission and/or entry into susceptible target cells. On the molecular level, our NMR spectroscopic studies show that ProLectin M binds relatively strongly to galectin-3, supporting the idea of an antagonist effect on the lectin.

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Section: Discussionmentioning

confidence: 99%

Carbohydrate prolectin-M, a galectin-3 antagonist, blocks SARS-CoV-2 activity

Sigamani¹,

Chen-Walden²,

Pahan³

et al. 2022

ijhs

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“…VOC/VOI likely increase in frequency due to positive selection, since all sites showing amino acid changes at the S protein of VOC/VOI, with the exception of site 732, have been identified as positively-selected amino acid sites. These results are also surprising because carbohydrate binding, not taken into account here, is also known to be important for SARS-CoV-2 binding as well (see for instance [ 19 ]). Moreover, it is known that two trimeric S protein structures bind an ACE2 homodimer, and here we look at the binding of a single S protein to a single ACE2 protein.…”

Section: Discussionmentioning

confidence: 87%

“…This is the single entry point of SARS-CoV-2 since HeLa cells not expressing ACE2 cannot be infected by SARS-CoV-2 [ 18 ]. This result shows that ACE2 is required for cell entry but does not exclude other factors, such as carbohydrate binding, as being important as well (see for instance [ 19 ]). ACE2 is an integral membrane protein that is expressed in the heart, lungs, kidneys, and intestines, and is a key player in the renin–angiotensin system [ 17 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Predictive Models of within- and between-Species SARS-CoV-2 Transmissibility

Soares

Vieira

2022

Viruses

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Viruses from the Coronaviridae family have been reported to infect a large range of hosts, including humans. The latest human-infecting coronavirus, SARS-CoV-2, turned into a pandemic and subtypes with different transmissibility have appeared since then. The SARS-CoV-2 Spike (S) protein interacts with the angiotensin-converting enzyme 2 (ACE2) host receptor, and thus, in silico models, based on the structural features of the SARS-CoV-2 S protein–ACE2 receptor complex, as well as ACE2 amino acid patterns, may be used to predict the within- and between-species transmissibility of SARS-CoV-2 subtypes. Here, it is shown that at the beginning of the pandemic, the SARS-CoV-2 S protein was, as expected for a virus that just jumped the species barrier, ill-adapted to the human ACE2 receptor, and that the replacement of one SARS-CoV-2 variant by another is partially due to a better fitting of the S protein–human ACE2 complex. Moreover, it is shown that mutations that are predicted to lead to a better fit have increased in the population due to positive selection. It is also shown that the number of ACE2-interfacing residues is positively correlated with the transmissibility rate of SARS-CoV-2 variants. Finally, it is shown that the number of species that are susceptible to infection by SARS-CoV-2, and that could be a reservoir for this virus, is likely higher than previously thought.

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“…N-acetyllactosamine (LacNAc), speci cally β-d-galactopyranosyl-1,4-N-acetyl-dglucosamine, is a unique acyl-amino sugar and a critical structural unit in human milk oligosaccharides, an antigen component of many glycoproteins, and an active antiviral property for the development of effective drugs against viruses [49]. The 6-sulfo -N-acetyllactosamine was found to inhibit the binding of the SARS-CoV-2 spike protein S1 subunit with blood group A RBCs and reduce the interaction between the spike protein S1 subunit and Angiotensin-converting enzyme 2 (ACE2) in SARS-CoV-2 infection [50].…”

Section: Analysis Of Lc-tof-msmentioning

confidence: 99%

Comparative putative metabolites profiling of Tachypleus gigas and Carcinoscorpius rotundicauda hemocytes stimulated with lipopolysaccharide

Jasni

Wee

Ismail

et al. 2023

Preprint

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Horseshoe crabs are among the most studied invertebrates due to their unique, innate immune system and biological processes. The metabolomics study was conducted on lipopolysaccharide (LPS)-stimulated and non-stimulated hemocytes isolated from the Malaysian Tachypleus gigas and Carcinoscorpius rotundicauda. LC-TOF-MS, multivariate analyses, Principal Component Analysis (PCA), and Partial least squares-discriminant analysis (PLS-DA) were included in this study to profile the metabolites. A total of 37 metabolites were identified to be differentially abundant and were selected based on VIP>1. However, of the 37 putative metabolites, only 23 were found to be significant with ANOVA at p< 0.05. The metabolites were identified using several databases, and the literature review of the metabolites was reported in the manuscript. Thus, this study has provided further insights into the putative metabolites' presence in the hemocytes of horseshoe crabs that are stimulated and non-stimulated with LPS and their abundance in each species. Several putative metabolites showed they have medicinal values from previous studies.

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Carbohydrate Ligands for COVID-19 Spike Proteins

Cited by 10 publications

References 79 publications

Carbohydrate prolectin-M, a galectin-3 antagonist, blocks SARS-CoV-2 activity

Carbohydrate prolectin-M, a galectin-3 antagonist, blocks SARS-CoV-2 activity

Predictive Models of within- and between-Species SARS-CoV-2 Transmissibility

Comparative putative metabolites profiling of Tachypleus gigas and Carcinoscorpius rotundicauda hemocytes stimulated with lipopolysaccharide

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