Comment on: Concerns of using sialidase fusion protein as an experimental drug to combat seasonal and pandemic influenza

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Abstract
Sir, Zhang1 questioned the validity of developing a sialidase fusion protein (DAS181) as an experimental drug against influenza. He raised two main concerns—first, that sialidase treatment would result in a greater chance of bacterial infection by exposing novel cryptic binding sites to bacterial pathogens and second, that influenza virus (IFV) receptors may be different from sialic acids (SA); thus, sialidase treatment may be ineffective. Although we agree with Zhang that the safety and efficacy of any novel therapeutic candidate, including DAS181, needs to be evaluated cautiously, statements made by him on sialidase treat- ment and the general view presented on the role of SA in IFV infection are either incomplete or incorrect. We thus offer the following corrections. It is known that IFV infection is associated with an increased risk of secondary infection by Streptococcus pneumoniae.2 A clear distinction that needs to be made, however, is whether the secondary S. pneumoniae infection arises from viral neuramini- dase (a sialidase) by itself or from the secondary effects of IFV infection. Scientific evidence clearly supports the latter, as influ- enza infection in the trachea and bronchus causes much deeper changes to the airway epithelium than could be caused by treat- ment of the epithelial cell surface with a sialidase. Influenza infection in humans results in extensive denudation of the ciliated epithelial cells down to the basal cells, or even to the