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

Abstract

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 PA_N and PA_N–I38T mutant in the primary screening. Dose-dependent inhibition assay showed that Epimedii folium can effectivity inhibit the PA_N and PA_N–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 PA_N and PA_N–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.

Graphical Abstract

Keywords:

• Polymerase acidic endonuclease
• influenza A virus
• plant extracts
• virtual screening
• molecular dynamic simulation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant no. 81603459].