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This correspondence letter evaluates the drug sensitivity of currently circulating mpox virus isolates from 12 unrelated patients during the global outbreak. The authors tested tecovirimat, cidofovir, and brincidofovir on infected primary human foreskin fibroblasts (HFF) and keratinocytes (HFK), observing replication and cytopathic effects. All isolates exhibited mutations in viral DNA polymerase and F13L targets of the tested antivirals that were absent in previous reference strains. Despite these genomic alterations, the isolates remained sensitive to the drugs, with IC50 values falling within therapeutic plasma ranges. The findings stress the importance of physiologically relevant cell models and suggest continued efficacy of current antiviral treatments.