title: Norovirus drug candidates that inhibit viral capsid attachment to human histo-blood group antigens.
abstract: Human noroviruses are the leading causative agents of epidemic and sporadic viral gastroenteritis and childhood diarrhoea worldwide. Human histo-blood group antigens (HBGA) serve as receptors for norovirus capsid protein attachment and play a critical role in infection. This makes HBGA-norovirus binding a promising target for drug development. Recently solved crystal structures of norovirus bound to HBGA have provided a structural basis for identification of potential anti-norovirus drugs and subsequently performed in silico and in vitro drug screens have identified compounds that block norovirus binding and may thereby serve as structural templates for design of therapeutic norovirus inhibitors. This review explores norovirus therapeutic options based on the strategy of blocking norovirus-HBGA binding.
authors.affiliation: School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors.forename: Eunüs S
authors.initials: ES
authors.lastname: Ali
authors.affiliation: Vaxine Pty Ltd, Flinders Medical Centre/Flinders University, Adelaide, South Australia, Australia.
authors.forename: Harinda
authors.initials: H
authors.lastname: Rajapaksha
authors.affiliation: Department of Microbiology & Infectious Diseases, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Carr
authors.affiliation: School of Medicine, Flinders University, Adelaide, South Australia, Australia; Vaxine Pty Ltd, Flinders Medical Centre/Flinders University, Adelaide, South Australia, Australia. Electronic address: nikolai.petrovsky@flinders.edu.au.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D001789:Blood Group Antigens / Q000737:chemistry / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism*; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D029322:Norovirus / Q000187:drug effects* / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D001789:Blood Group Antigens; D036022:Capsid Proteins; D011991:Receptors, Virus
keywords: Antiviral therapy; Binding inhibitors; Human histo-blood group antigen; Norovirus; Norovirus capsid proteins