Evaluation of combining the PDX analogue AN-137B with oseltamivir in a mouse model of severe influenza A (H1N1) infection

Severe influenza infections involve an exacerbation of the pro-inflammatory response, which is influenced by both viral and host factors. Protectins PD1 and PDX previously demonstrated anti-influenza activity as well as anti-inflammatory properties. We recently reported that the combination of AN-137B, a molecular analogue of PDX, with oseltamivir or baloxavir provided synergism/additive effects against influenza, <i>in vitro</i>. Herein, we investigated potential benefits of the AN-137B-oseltamivir combination in mice infected with influenza A/Puerto Rico/8/1934 (H1N1) virus. Untreated animals and those that received single oseltamivir or AN-137B treatment showed mortality rates of 80%, 100% and 100%, respectively, whereas only 40% of mice that received the oseltamivir-AN-137B combination had to be euthanized. Body weight loss was also lower in the group of the combination. In the latter group, the mean lung viral titre (LVT), as determined by plaque assay (2.53 ± 0.63 × 10⁵ PFU/mL) and by qRT-PCR (2.39 ± 1.3 × 10⁸ copies/mL), was significantly lower than that of the untreated group (4.76 ± 0.9 × 10⁵ PFU/mL and 3.75 ± 0.86 × 10⁸ copies/mL (<i>p</i> < .05), contrasting with LVTs of animals that received single therapies. These <i>in vivo</i> results reinforce the potential of AN-137B when combined to a potent anti-influenza agent against severe influenza.