Antimalarial cabamiquine inhibits blood-stage of different field isolates of Plasmodium species

Malaria remains a major public health concern in Sub-Saharan Africa. The widespread and emerging drug resistance calls for urgent development of new drugs with novel modes of action to treat, control, and eliminate malaria. Cabamiquine, a promising antimalarial drug candidate that inhibits protein synthesis, has demonstrated promising potency across multiple life stages of P. falciparum. Here, in Ghana and Mali, we assessed the ex-vivo susceptibility of non-falciparum malaria field isolates of P. ovale and P. malariae to cabamiquine, in comparison to P. falciparum and explored the candidate drugs potential cross-resistance with existing antimalarial drugs. Thus, cabamiquine susceptible and selected resistant P. falciparum laboratory strains and field isolates were tested against a panel of antimalarial drugs. P. ovale isolates displayed a decreased susceptibility to DHA (median IC50 = 3.962 nM; IC50 range of 0.6587 to 9.154 nM) when compared to P. falciparum (p = 0.0371), but no significant difference was noticed for cabamiquine against both species (P. ovale: median IC50 = 0.9441 nM; IC50s ranged of 0.225 to 2.315 nM). Conversely, P. malariae isolates were less susceptible to cabamiquine (median IC50 = 3.915 nM; range 1.410 to 7.010) compared with P. falciparum (p = 0.001). There was no difference in susceptibility to DHA, both for P. malariae (median IC50 = 7.641 nM; range of 2.510 to 1268 nM) and P. falciparum isolates. With regards to the cabamiquine-resistant parasites (wild-type (WT) and mutants), there was limited variation between their susceptibilities to amodiaquine, tafenoquine, sulfadoxine, pyrimethamine, pyronaridine, active amodiaquine, lumefantrine, pyrimethamine, chloroquine, primaquine, and quinine. Overall, P. ovale and P. malariae are susceptibility to cabamiquine.