Antiviral effect of a nucleic acid hydrolyzing scFv against oseltamivir resistant influenza A virus

Abstract

Influenza viral genome is frequently mutated due to antigenic shift and drift, and therefore the existing antiviral drugs have been suffered from low efficacy against the viruses. Here we report an innovative strategy for treating influenza Type A (IAV) infection by 3D8 single chain variable fragment (scFv) showing intrinsic viral RNA hydrolyzing activity, cell penetration activity and the epidermal cell penetration ability. In this study, we first analyzed antiviral activity directed by 3D8 scFv to three different strains, two oseltamivir-sensitive (A/PuertoRico/8/1934, A/X-31) and oseltamivir-resistant (A/Korea/2785/2009pdm) using cell culture models, suggesting that 3D8 scFv reduces viral genomic RNA. Moreover, we further addressed antiviral effect to analyze clinical outcomes in in vivo mice model. Intranasal administered 3D8 scFv rescued the mice challenged by oseltamivir resistant H1N1. Consistent results are observed through IHC pathology and molecular virological analysis. Taken together, these results demonstrate that 3D8 scFv has antiviral potential against a wide range of IAV.