title: The use of sialidase therapy for respiratory viral infections.
abstract: DAS181 is an inhaled bacterial sialidase which functions by removing sialic acid (Sia) from the surface of epithelial cells, preventing attachment and subsequent infection by respiratory viruses that utilize Sia as a receptor. DAS181 is typical of bacterial sialidases in cleaving Sia α2-3 and Sia α2-6 linkages, and it also has a demonstrated effect against acetylated and hydroxylated forms of Sia. The potency of the compound has been enhanced by coupling the active sialidase with an amphiregulin tag, allowing a longer duration of action and minimizing spread to the systemic circulation. DAS181 is now in Phase II development for the treatment of influenza, and it has also demonstrated activity in individual cases of parainfluenza in immunosuppressed patients. Continued evaluation of the roles and activities of bacterial sialidases is required to expand the range of successful antiviral therapies targeting Sia or its derivatives.
authors.affiliation: Department of Pathology, The University of Hong Kong, Pok Fu Lam, Hong Kong. nicholls@pathology.hku.hk
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Moss
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
mesh_terms: D000107:Acetylation; D066258:Amphiregulin; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D066255:EGF Family of Proteins; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009439:Neuraminidase / Q000737:chemistry / Q000627:therapeutic use*; D010252:Paramyxoviridae / Q000472:pathogenicity; D018184:Paramyxoviridae Infections / Q000188:drug therapy; D011991:Receptors, Virus / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use*; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000821:virology*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D000998:Antiviral Agents; D001426:Bacterial Proteins; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C525612:oplunofusp; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid