The Design, Synthesis and Assessment of Novel Haemagglutinin- Neuraminadase Inhibitors

Abstract

The human parainfluenza viruses (hPIV) are leading causes of respiratory disease in young children, the immunocompromised and the elderly. All subtypes can cause lower and upper respiratory disease. The surface of human parainfluenzza virus and a number of other paramyxoviruses contains, amongst other biomolecules, a multifunctional glycoprotein known as haemagglutinin-neuraminidase (HN). The HN has three roles in viral pathogenesis; the binding to terminally bound sialic acid residues of cell oligosaccharides, thereby mediating viral attacment to the host cell; the promotion of viral and host cell fusion; and the cleavage of cell surface sialic acids to promote viral elution from host cells. The important role of HN in the viral life-cycle makes it an attractive target for therapeutic intervention. This thesis details an investigation into the design, synthesis and assessment of novel inhibitors of paramyxoviral haemagglutinin-neuraminidase.