Daily Mosnodenvir as Dengue Prophylaxis in a Controlled Human Infection Model.

Area of Science:

• Virology
• Infectious Diseases
• Antiviral Research

Background:

• Dengue affects half the global population, with no available antiviral treatments.
• Current dengue prevention relies on vector control and supportive care.

Purpose of the Study:

• To evaluate the efficacy and safety of oral mosnodenvir against dengue virus type 3 (DENV-3) in a controlled human infection model.
• To determine the optimal dosage of mosnodenvir for antiviral activity.

Main Methods:

• A phase 2a, double-blind, randomized trial involving healthy adults challenged with an underattenuated DENV-3 strain.
• Participants received oral mosnodenvir at low, medium, or high doses, or placebo.
• Primary endpoint: DENV-3 RNA load (log10 AUC D1-29); secondary endpoints: safety, pharmacokinetics, virologic and serologic features.

Main Results:

• High-dose mosnodenvir resulted in 60% of participants being infection-free, compared to 0% for placebo.
• Significantly lower DENV-3 RNA load (log10 AUC D1-29) was observed with high-dose mosnodenvir versus placebo (P<0.001).
• No serious adverse events were reported; viral NS4B variations emerged in mosnodenvir recipients.

Conclusions:

• High-dose oral mosnodenvir demonstrated significant reduction in DENV-3 RNA load in a controlled human infection model.
• Mosnodenvir was safe and well-tolerated, with no serious adverse events.
• Further investigation into mosnodenvir as a potential dengue therapeutic is warranted.