Combination therapies
have emerged to mitigate
Plasmodium
drug resistance,
which has hampered the fight against malaria. M5717
is a potent multistage antiplasmodial drug under clinical development,
which inhibits parasite protein synthesis. The combination of M5717
with pyronaridine, an inhibitor of hemozoin formation, displays potent
activity against blood stage
Plasmodium
infection.
However, the impact of this therapy on liver infection by
Plasmodium
remains unknown. Here, we employed a recently
described 3D culture-based hepatic infection platform to evaluate
the activity of the M5717-pyronaridine combination against hepatic
infection by
P. berghei
. This effect was further
confirmed
in vivo
by employing the C57BL/6J rodent
Plasmodium
infection model. Collectively, our data demonstrate
that pyronaridine potentiates the activity of M5717 against
P. berghei
hepatic development. These preclinical results
contribute to the validation of pyronaridine as a suitable partner
drug for M5717, supporting the clinical evaluation of this novel antiplasmodial
combination therapy.
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