Post-translational modifications of coronavirus proteins: roles and function

Fung, To Sing; Liu, Ding Xiang

The functional implication of PTMs on many coronavirus proteins has not been fully characterized, and their biological significance requires further investigations combining reverse genetics and suitable in vivo models. However, the presence of multiple modification sites on some functionally important domains of a protein, as examplified by the presence of more than 20 predicted N-linked glycosylation sites on various functional domains of coronavirus S protein and multiple phosphorylation sites in coronavirus N protein, and the absence of sensitive and specific methods for detection of individual PTMs in live cells and infectious particles have hindered further investigation into the function of PTMs at a specific site of a coronavirus protein in virus replication and pathogenesis. In addition, it appears that the functional effect of mutation at a canonical site can be compensated by the same PTM at an alternate site. This is especially true for proteins with multiple sites for a certain PTM, such as N-linked glycosylation of S protein and phosphorylation of N protein.