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

  • PLoS Comput Biol. 2023 Dec 6;19(12):e1011662. doi: 10.1371/journal.pcbi.1011662.
Clare P McCormack  1 ,  Olivia Goethals  2 ,  Nele Goeyvaerts  3 ,  Xavier D Woot de Trixhe  3 ,  Peggy Geluykens  3  4 ,  Doortje Borrenberghs  2 ,  Neil M Ferguson  1 ,  Oliver Ackaert  3 ,  Ilaria Dorigatti  1
Affiliations
  • 1. MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom.
  • 2. Janssen Global Public Health, Janssen Pharmaceutica NV, Beerse, Belgium.
  • 3. Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.
  • 4. Discovery, Charles River Beerse, Beerse, Belgium.
PMID: 38055683 DOI: 10.1371/journal.pcbi.1011662
Abstract

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.

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