Modelling the impact of JNJ-1802, a first-in-class dengue inhibitor blocking the NS3-NS4B interaction, on in-vitro DENV-2 dynamics

Dengue virus (DENV) is a public health challenge across the tropics and subtropics. Currently, there is no licensed prophylactic or antiviral treatment for dengue. The novel DENV inhibitor JNJ-1802 can significantly reduce viral load in mice and non-human primates. Here, using a mechanistic viral kinetic model calibrated against viral RNA data from experimental in-vitro infection studies, we assess the in-vitro inhibitory effect of JNJ-1802 by characterising infection dynamics of two DENV-2 strains in the absence and presence of different JNJ-1802 concentrations. Viral RNA suppression to below the limit of detection was achieved at concentrations of >1.6 nM, with a median concentration exhibiting 50% of maximal inhibitory effect (IC50) of 1.23x10-02 nM and 1.28x10-02 nM for the DENV-2/RL and DENV-2/16681 strains, respectively. This work provides important insight into the in-vitro inhibitory effect of JNJ-1802 and presents a first step towards a modelling framework to support characterization of viral kinetics and drug effect across different host systems

Computerising: lessons from the DHSS pensions strike

Personnel specialists from both employers and unions should be given, or, if necessary, should seize influential roles in the planning and implementing stages of computerisation projects. The seven-month “Pensions Strike” at the Department of Health and Social Security centre in Newcastle which cost more than £150 million is assessed, revealing that deficiencies in planning the introduction of new technology, limited objectives, and the failure to understand the industrial relations and personnel implications of those plans will crucially show up at the implementation stage