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We are using molecular, cellular and structural biology to understand the structure and function of proteins involved in pathogenesis with a view to developing new drugs against a range of disease caused by microorganisms. The sialidase (or neuraminidase) superfamily are virulence factors in influenza, parainfluenza, cholera and pneumonia. Our structural studies on the paramyxovirus hemagglutinin-neuraminidase (HN) has led to the structure-based development of a new drug that is a potential treatment for childhood parainfleunza. We are currently studying the sialidases from Streptococcus pneumoniae and Pseudomonas aeruginosa, and developing inhibitors against these enzymes that are key virulence facotrs in the respiratory diseases caused by these bacteria.
More recently, we have engineered mutlivalent forms of a couple of carbohydrate-binding modules specific for sialic acid, a key component of the receptor used by the influenza virus, parainfluenza virus, some coronaviruses and pneumococci. Experients in mice using lethal viral challenges show that these mutlivalent bioloigcs have great potential as a prophylactic for the prevention of certain respiratory diseases.
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