The impact of the butterfly effect on human parainfluenza virus haemagglutinin-neuraminidase inhibitor design.

ABSTRACT: Human parainfluenza viruses represent a leading cause of lower respiratory tract disease in children, with currently no available approved drug or vaccine. The viral surface glycoprotein haemagglutinin-neuraminidase (HN) represents an ideal antiviral target. Herein, we describe the first structure-based study on the rearrangement of key active site amino acid residues by an induced opening of the 216-loop, through the accommodation of appropriately functionalised neuraminic acid-based inhibitors. We discovered that the rearrangement is influenced by the degree of loop opening and is controlled by the neuraminic acid's C-4 substituent's size (large or small). In this study, we found that these rearrangements induce a butterfly effect of paramount importance in HN inhibitor design and define

SUBMITTER: Dirr L 

PROVIDER: S-EPMC5495814 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature