Potent HCV NS3 Protease Inhibition by a Water-Soluble Phyllanthin Congener.

ABSTRACT: NS3/4A protease of hepatitis C virus (HCV) plays an important role in viral RNA replication. A 1,4-diphenylbutanedicarboxylic acid derivative, namely, phyllanthin, extracted from the leaf of a herbal plant, Phyllanthus amarus, inhibits HCV NS3/4A protease and replication activities. However, the reduced aqueous solubility, high toxicity, and poor oral bioavailability are major impediments with phyllanthin. We herein present a design approach to generate phyllanthin congeners in order to potentiate inhibition activity against protease. The phyllanthin congeners were synthesized by chemical methods and subjected to systematic biological studies. One of the congeners, annotated as D8, is identified as a novel and potent inhibitor of the HCV-NS3/4Aprotease activity in vitro

SUBMITTER: B UR 

PROVIDER: S-EPMC7254805 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature