Work

Intervention timing and disease stage shape tecovirimat and cidofovir efficacy in male SCID mice

Year: 2025

Type: article

Abstract: On February 27, 2025, WHO maintained monkeypox as a PHEIC following its third round of assessment. Human monkeypox virus infection primarily manifests with fever, lymphadenopathy, and rash. Severe cases may develop pneumonia, encephalitis, myocarditis and arthritis. After evaluation of three murine models (ICR, IFNAR1 −/− , and SCID), we identified SCID mice as stable hosts for clade IIb, modeling high-risk populations like patients with HIV. Three models, characterized by rash, pneumonia, and arthritis, were established for the pharmacodynamic evaluation of tecovirimat and cidofovir. Both drugs decreased virus titer in target organs during early infection and ensured 100% survival. As a limitation, cidofovir failed to inhibit viral DNA load in skin lesions, and monotherapy of cidofovir or tecovirimat was ineffective in prolonged intradermal infections. These data indicate that the therapeutic efficacy of tecovirimat and cidofovir is contingent upon distinct disease phenotypes and progression stages, underscoring the necessity for novel therapeutic interventions against monkeypox.

Source: Nature Communications

DOI: 10.1038/s41467-025-67548-0