Therapeutic potential of protectins against influenza infections

Although antivirals that inhibit neuraminidase and polymerase of influenza A and B viruses exist, these modalities have proven relatively ineffective in treating severe forms of infection. Indeed, in this setting, mortality is attributable not only to viral replication but also to a disproportionate inflammatory response called a 'cytokine storm'. In our research program, we aim to confirm the hypothesis that the combination of a classical antiviral targeting a viral protein combined with an immunomodulator decreasing the uncontrolled inflammatory response of the host is more effective in reducing mortality than either compound alone. More specifically, we will evaluate in mouse and ferret models of viral infection analogs of protectin DX (PDX), a natural molecule derived from docosahexaenoic acid (DHA), which is a polyunsaturated fatty acid of the omega-3 type. Protectins have the ability to participate in the resolution of inflammation, thus promoting the return to homeostasis of the affected tissue. These molecules therefore have the potential to become an adjunct treatment in patients with severe influenza and possibly in cases of other respiratory viral infections that can lead to a disproportionate inflammatory response (such as the SARS-CoV-2 virus causing COVID-19).