Comparison of Baloxavir-Based Combinations and Monotherapies for Treating Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Mice

The study compared the efficacy of single drugs and two-drug combinations for treating severe influenza A(H5N1) virus infection in mice. Three antiviral drugs were tested: oseltamivir (neuraminidase inhibitor), baloxavir (cap-dependent endonuclease inhibitor), and molnupiravir (nucleoside analog). Mice were infected intranasally and treatment began 6 hours after infection. At low doses, oseltamivir and molnupiravir monotherapies provided partial protection (2 of 7 mice survived), while baloxavir was more effective (4 of 7 mice survived). Baloxavir-containing combination regimens showed the greatest protection with 100% survival (7 of 7 mice) and stabilized body weight. The results indicate that combination regimens containing baloxavir are more effective than monotherapies for treating H5N1 infection.