Structural biology of dengue virus enzymes: towards rational design of therapeutics.

Abstract:

:Development of anti-dengue therapy represents an urgent un-met medical need. Towards antiviral therapy, recent advances in crystal structures of DENV enzymes have led to the possibility of structure-based rational design of inhibitors for anti-dengue therapy. These include (i) the structure of the 'active' form of the DENV protease in complex with a peptide substrate; (ii) the structure of DENV methyltransferase bound to an inhibitor that selectively suppresses viral methyltransferase, but not human methyltransferases; (iii) the structure of DENV RNA-dependent RNA polymerase in complex with a small-molecule compound. This review summarizes the structural biology of these three key enzymes (protease, methyltransferase, and polymerase) that are essential for DENV replication. The new structural information has provided new avenues for development of anti-dengue therapy.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Noble CG,Shi PY

doi

10.1016/j.antiviral.2012.09.007

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

115-26

issue

2

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(12)00204-5

journal_volume

96

pub_type

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