Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37–Viruses That Cause Highly Contagious Eye Infections

Johansson, E. Susanne; Caraballo, Rémi; Mistry, Nitesh; Zocher, Georg; Qian, Weixing; Andersson, Christian; Hurdiss, Daniel L.; Chandra, Naresh; Thompson, Rebecca; Frängsmyr, Lars; Stehle, Thilo; Arnberg, Niklas; Elofsson, Mikael

doi:10.1021/acschembio.0c00446

Cited by 15 publications

(43 citation statements)

References 41 publications

(138 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an ongoing research project, we were interested in studying the potential of 4-O-alkyl analogs of 5 (Figure 1) as probes targeting cell attachment during adenovirus [31][32][33] and coxsackievirus infections 34,35 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 4-O-Alkylated N-Acetylneuraminic Acid Derivatives

Johansson¹,

Caraballo²,

Elofsson

2020

Preprint

Self Cite

View full text Add to dashboard Cite

N-acetyl neuraminic acid (Neu5Ac) is a densely functionalized nine-carbon monosaccharide. It ubiquitously decorates the surface of mammalian cells were it is found in terminal positions of glycolipids and glycoproteins. This important saccharide and natural analogs play important roles in a number of processes in health and disease. Despite this few Neu5Ac based therapeutics have been developed. To further study and understand the chemistry and biology of Neu5Ac efficient protocols for synthesis of the parent natural compounds as well as synthetic analogs are required. In the manuscript, we report investigation of alkylation reactions to produce selectively modified Neu5Ac with focus on position 4. The study provides insights in the reaction and we establish robust protocols that allow selective modification of Neu5Ac for use as tool compounds and starting points for drug discovery.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of 4-O-Alkylated N-Acetylneuraminic Acid Derivatives

Johansson¹,

Caraballo²,

Elofsson

2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…These studies used the same SV40 immortalized corneal epithelial cell line [ 48 ] discussed above. Subsequent work showed that some but not all of the EKC-associated HAdVs bind to sialic acid-expressing cell surface glycans [ 85 ], and that various multivalent sialic acid constructs could block binding [ 84 , 86 , 87 , 88 , 89 , 90 , 91 ]. Sites on the fiber knob that bind to the various potential adenovirus receptors have been mapped in exquisitely detailed structural studies [ 92 ].…”

Section: Corneal Epithelial Cell Tropism and Receptorsmentioning

confidence: 99%

Adenovirus and the Cornea: More Than Meets the Eye

Rajaiya

Saha

Ismail

et al. 2021

Viruses

View full text Add to dashboard Cite

Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of conjunctivitis. One site of infection that has received sparse attention is the cornea, a transparent tissue and the window of the eye. While most adenovirus infections are self-limited, corneal inflammation (keratitis) due to adenovirus can persist or recur for months to years after infection, leading to reduced vision, discomfort, and light sensitivity. Topical corticosteroids effectively suppress late adenovirus keratitis but are associated with vision-threatening side effects. In this short review, we summarize current knowledge on infection of the cornea by adenoviruses, including corneal epithelial cell receptors and determinants of corneal tropism. We briefly discuss mechanisms of stromal keratitis due to adenovirus infection, and review an emerging therapy to mitigate adenovirus corneal infections based on evolving knowledge of corneal epithelial receptor usage.

show abstract

“…Binding and infection experiments using corneal cells indicate that the cell surface receptor used by CVA24v is composed of a sialylated disaccharide (Neu5Acα2,3Gal) on O-glycosylated proteins ( 29 ). Consequently, derivatives based on sialic acid have been developed and shown to be effective in preventing HAdV-D37 and CVA24v binding and infection of human corneal epithelial cells ( 30 , 31 ).…”

Section: The Glycocalyx In Ocular Surface Infectionmentioning

confidence: 99%

The Epithelial Cell Glycocalyx in Ocular Surface Infection

2021

View full text Add to dashboard Cite

The glycocalyx is the main component of the transcellular barrier located at the interface between the ocular surface epithelia and the external environment. This barrier extends up to 500 nm from the plasma membrane and projects into the tear fluid bathing the surface of the eye. Under homeostatic conditions, defense molecules in the glycocalyx, such as transmembrane mucins, resist infection. However, many pathogenic microorganisms have evolved to exploit components of the glycocalyx in order to gain access to epithelial cells and consequently exert deleterious effects. This manuscript reviews the implications of the ocular surface epithelial glycocalyx to bacterial, viral, fungal and parasitic infection. Moreover, it presents some ongoing controversies surrounding the functional relevance of the epithelial glycocalyx to ocular infectious disease.

show abstract

Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37–Viruses That Cause Highly Contagious Eye Infections

Cited by 15 publications

References 41 publications

Synthesis of 4-O-Alkylated N-Acetylneuraminic Acid Derivatives

Synthesis of 4-O-Alkylated N-Acetylneuraminic Acid Derivatives

Adenovirus and the Cornea: More Than Meets the Eye

The Epithelial Cell Glycocalyx in Ocular Surface Infection

Contact Info

Product

Resources

About