Antiviral-effect of nitrogen-containing compounds isolated from Sarcodon imbricatus on influenza A virus through regulation of ZBP-1 mediated necroptosis

Abstract

This study focuses on the elucidation of the structure and antiviral properties of six nitrogen-containing compounds including amino acid derivates (1 and 2) and heterocyclic compounds (3-6) isolated from the fruiting bodies of Sarcodon imbricatus, particularly Compound 2, an (S)-2-(hydroxyimino)-3-methylpentanoic acid ethyl ester. Their antiviral effects were tested against influenza A virus (IAV) in A549 cells. Particularly, Compound 2 exhibited significant antiviral activity in post-treatment assays, reducing viral protein expression and inhibiting viral replication with an IC₅₀ of 14.9 μmol/L. Additionally, it demonstrated anti-inflammatory effects by reducing levels of cytokines such as TNF-α, IL-6 and IL-1β as well as the oxidative stress induced by IAV infection, while inhibiting necroptosis, a form of programmed cell death associated with inflammation. Thus, our findings demonstrate the antiviral and anti-inflammatory properties of Compound 2, making it a promising candidate for further research as an anti-influenza agent.

Keywords: Influenza A; Necroptosis; Nitrogen-containing compounds; Sarcodon imbricatus; ZBP-1.