Title:The RNA-Dependent-RNA Polymerase, an Emerging Antiviral Drug Target for the Hendra Virus
Volume: 15
Issue: 1
Author(s): Tony Velkov, Vincenzo Carbone, Jesmin Akter, Sivashangarie Sivanesan, Jian Li, Travis Beddoe and Glenn A. Marsh
Affiliation:
Keywords:
Drug, hendra virus, RNA-dependent-RNA polymerase, L protein, P protein, paramyxoviruses.
Abstract: Australia is facing a major national medical challenge with the emergence of the Hendra virus (HeV) as a
medically and economically important pathogen of humans and animals. Clinical symptoms of human HeV infection can
include fever, hypotension, dizziness, encephalitis, respiratory haemorrhage and edema. The window of opportunity for
successful patient treatment remains unknown, but is likely to be very narrow. Currently, very few effective therapeutic
options are available for the case management of severe HeV infections or the rapid silencing of local outbreaks. This underscores
the need for more activity in the drug discovery arena to develop much needed therapeutics that specifically targets
this deadly disease. The structural analysis of HeV is very much in its infancy, which leaves many gaps in our understanding
of the biology of HeV and makes structure-guided drug design difficult. Structural studies of the viral RNAdependent-
RNA polymerase (RdRp), which is the heart of the viral replication machinery, will set the stage for rational
drug design and fill a major gap in our understanding of the HeV replication machinery. This review examines the current
knowledge based on the multi-domain architecture of the Hendra RdRp and highlights which essential domain functions
represent tangible targets for drug development against this deadly disease.
