Klaus Klumpp

TL;DR: Hepatitis C virus (HCV) polymerase activity is essential for HCV replication and the corresponding 5′-triphosphate derivative (R1479-TP) is a potent inhibitor of native HCV replicase isolated from replicon cells and of recombinant HCV polymerase (NS5B)-mediated RNA synthesis activity.

TL;DR: Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in d Dengue and provides the field with a clinically evaluated benchmark molecule.

TL;DR: A series of small molecule N-hydroxyimides was identified with significant enzyme inhibitory potency and selectivity for HIV RNase H, consistent with a two-metal ion mechanism of RNA cleavage as previously suggested for a number of polymerase-associated nucleases.

TL;DR: These findings demonstrate the selection of replicon variants dually resistant to two NS5B polymerase inhibitors binding to different sites of the enzyme, and provide initial insights into the in vitro mutational threshold of the HCV NS5 B polymerase and the potential impact of viral fitness on theselection of multiple-resistant mutants.

TL;DR: The crystal structure provides understanding of a drug efficacy mechanism related to the induction and stabilization of protein–protein interactions and enables structure-guided design to improve antiviral potency and drug-like properties.