Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment.
Biochemistry
; 60(13): 999-1018, 2021 04 06.
Article
in English
| MEDLINE | ID: covidwho-889110
ABSTRACT
Carbohydrate-receptor interactions are often involved in the docking of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered "undruggable", meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs), small molecules that bind carbohydrates, could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of SCRs, and recent results demonstrating their ability to prevent viral infections in vitro. Common SCR design strategies based on boronic ester formation, metal chelation, and noncovalent interactions are discussed. The benefits of incorporating the idiosyncrasies of natural glycan-binding proteins-including flexibility, cooperativity, and multivalency-into SCR design to achieve nonglucosidic specificity are shown. These studies into SCR design and binding could lead to new strategies for mitigating the grave threat to human health posed by enveloped viruses, which are heavily glycosylated viroids that are the cause of some of the most pressing and untreatable diseases, including HIV, Dengue, Zika, influenza, and SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Receptors, Virus
/
Drug Design
/
Virus Attachment
/
Small Molecule Libraries
/
Receptors, Artificial
Limits:
Animals
/
Humans
Language:
English
Journal:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Acs.biochem.0c00732
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