Bilobetin, a novel small molecule inhibitor targeting influenza virus polymerase acidic (PA) endonuclease was screened from plant extracts.

The influenza A virus polymerase acidic (PA) endonuclease is an attractive target for anti-influenza drug development. In this study, plant extracts were used to screen the inhibitor against the PA endonuclease and its mutant. In 45 kinds of plant extracts, eight can effectively inhibit the PAN and PAN-I38T mutant in the primary screening. Dose-dependent inhibition assay showed that Epimedii folium can effectivity inhibit the PAN and PAN-I38T with IC50 of 11.23 and 26.03 μM, respectively. Furthermore, 130 ingredients of E. folium were virtually screened using the in silico method, and the compounds ginkgetin and bilobetin bind to the active pocket of PAN and PAN-I38T with a strong interaction force. Gel-based PA endonuclease analysis and inhibition type analysis identified that bilobetin can competitively inhibit the PA. Hence, bilobetin, as an ingredient of E. folium, was screened through in vitro and in silico research.