Deoxy-Mannose Derivatives as Potential Immune System Boosters in SARS-CoV-2 Infections
Résumé
Coronaviruses such as SARSCoV-2 are spherical infectious agents covered with out-pointing protein spicules. These spicules are coated with the host's glycans that display immunoevasion epitopes in the circulating medium of the infected body. The post-transcriptional construction of this external camouflaging glycan envelope provides the virus with an elusive protection from the immune system. The poly-mannose glycans are synthesized in the infected cells' endoplasmic reticulum and transferred onto the S-protein N-glycosylation sites of the spicules at the end of the virus reproduction cycle. The core structure of these glycans is composed of branched mannoses on an asparagine N-glycosylated chitobiose root. Deoxy-D-mannoses and derivatives such as fluoro-or chloro-substituted analogues possess the structural features to be potentially recognised and used by cytoplasm or endoplasmic reticulum oligo-mannose synthase enzymes during the construction of the dolichol-phosphate glycan biosynthesis. If incorporated onto the growing chitobiose rooted disaccharide, these residues would inhibit further growth of the terminal poly-mannose structure by introducing-OH glycosylation site deficiencies at key branching or elongating positions. These deficiencies would then prevent full growth of the oligo-mannose terminal glycan. The presence of shorter and incomplete glycan epitopes on the released virus spicules would leave a larger surface of the S-protein uncovered. Consequently, the virus antigenic sites would be more exposed (accessible) to the circulating antibodies of the host's immune system.
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