AbstractAntiviral drugs are powerful tools to combat emerging viral diseases, one of the leading causes of morbidity and mortality in the world. However, most existing antivirals have failed to cure COVID-19. Accordingly, there is an urgent need for new therapeutics with powerful antiviral and tolerable side effects. Here, we observed that recombinant human interferon-alpha (IFNa) triggered cell intrinsic and extrinsic antiviral responses and reduced replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human lung epithelial Calu-3 cells. However, IFNa alone was insufficient to completely abolish SARS-CoV-2 replication. The combinations of IFNa with camostat, remdesivir, EIDD-2801, cycloheximide or convalescent serum showed strong synergy and, therefore, effectively inhibited SARS-CoV-2 infection. Additionally, we demonstrated synergistic antiviral activity of IFNa2a with pimodivir against influenza A virus (FluAV) infection in human lung epithelial A549 cells, as well as IFNa2a with lamivudine against human immunodeficiency virus 1 (HIV-1) infection in human TZM-bl cells. Our results indicate that IFNa2a-based combinational therapies help to reduce drug dose and improve efficacy in comparison with monotherapies, making them attractive targets for further pre-clinical and clinical development. Additionally, they have powerful treatment potential, and can be leveraged for use in the inhibition of not only emerging or re-emerging viruses, but also immune-evading or drug-resistant viral variants, and viral co-infections.
Intranasal Administration of Chitosan Against Influenza A (H7N9) Virus Infection in a Mouse Model
