Glycoprotein endo-alpha-1,2-mannosidase (MANEA)

Glycoprotein endo-alpha-1,2-mannosidase (MANEA) is a human enzyme located in the Golgi apparatus, encoded by the MANEA gene. It is the sole endo-acting glycoside hydrolase that mediates a glucosidase-independent pathway for N-glycan maturation by trimming glucosylated mannose residues from glycoproteins. MANEA enables glycoproteins that escape endoplasmic reticulum (ER) glucosidase trimming to undergo processing, affecting glycoprotein folding, trafficking, and recognition. This function is central to secretory pathways and has important implications in viral pathogenesis, as many enveloped viruses rely on host glycosylation for their proteins. Structural studies show MANEA belongs to the glycoside hydrolase family 99 and catalyzes reactions with retention of substrate stereochemistry via an epoxide intermediate. It is considered a host-directed antiviral therapeutic target, and small molecule inhibitors against MANEA have demonstrated efficacy in reducing viral infectivity for viruses such as dengue and bovine viral diarrhea in cellular models. Ongoing research seeks to develop broad-spectrum antivirals based on MANEA inhibition, with attention to minimizing disruption of essential host glycoprotein functions.

Other names

MANEAENDOhEndomannosidase endo-alphaendo-alpha mannosidaseendomannosidasemandaselinglycoprotein endo-alpha-1,2-mannosidasealpha 1,2-endomannosidase

Inhibition of MANEA disrupts N-glycan processing, preventing proper glycoprotein maturation of viral glycans, thereby reducing viral infectivity. Mechanistic basis involves retention of substrate stereochemistry via epoxide intermediate formation during catalysis.