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

Currently, mpox virus (MPXV) continues to pose a global public health challenge, with immunocompromised individuals often exhibiting more severe clinical symptoms. This study screens three male mouse models (ICR, IFNAR1-/-, SCID) and identifies SCID mice as the optimal model for modeling severe patient symptoms, including pneumonia, rash, and localized inflammation, which is applied to evaluate the antiviral efficacy of tecovirimat and cidofovir. Both drugs prevent systemic MPXV spread when administered within two days post virus exposure. Local antiviral efficacy differs between the two drugs, particularly after intradermal infection. Prolonged treatment up to 28 days post infection results in 100% survival of SCID mice but fails to effectively suppress localized rash and inflammatory swelling, suggesting that the drugs have limited impact at later stages of the disease. These findings indicate that the therapeutic efficacy of tecovirimat and cidofovir depends on the timing of intervention initiation and the stage of disease progression. This study establishes MPXV clade IIb-infected SCID mouse models presenting with pneumonia, lesions, and localized inflammation that recapitulate key clinical manifestations observed in high-risk populations, and demonstrates that the timing of treatment initiation and the stage of disease progression critically influence the anti-MPXV efficacy of both tecovirimat and cidofovir.