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

Area of Science:

• Virology
• Immunology
• Pharmacology

Background:

• Mpox virus (MPXV) poses a global health risk, particularly to immunocompromised individuals.
• Severe clinical manifestations in immunocompromised patients necessitate effective therapeutic strategies.

Purpose of the Study:

• To identify an optimal mouse model for severe mpox virus infection.
• To evaluate the antiviral efficacy of tecovirimat and cidofovir in a relevant disease model.

Main Methods:

• Screening of three male mouse models: ICR, IFNAR1-/- , and SCID mice.
• Assessment of SCID mice for modeling severe MPXV symptoms like pneumonia, rash, and inflammation.
• Evaluation of tecovirimat and cidofovir efficacy based on administration timing and disease stage.

Main Results:

• SCID mice effectively model severe MPXV symptoms, including pneumonia, rash, and inflammation.
• Both tecovirimat and cidofovir prevent systemic MPXV spread if given within two days of exposure.
• Antiviral efficacy varies between drugs, especially after intradermal infection, with limited impact on late-stage localized symptoms.

Conclusions:

• SCID mice are a suitable model for severe MPXV infection, mimicking human patient symptoms.
• Early administration of tecovirimat and cidofovir is crucial for preventing systemic spread.
• Therapeutic success is contingent on the timing of intervention and the disease progression stage, with limited efficacy in later disease phases.