Highly Conjugated Ergosterols With Anti‐Influenza Virus Activity From the Marine‐Derived Fungus <i>Eutypella</i> Sp. F0219

One rare 15-nor-cadinane sesquiterpenoid (1), one new chromene amide derivative (2), and one new highly conjugated ergosterol steroid (3), along with three known compounds (4-6), were isolated from the marine-derived fungus Eutypella sp. F0219. Their chemical structures, including absolute configurations, were established by HR-ESIMS, extensive 1D and 2D NMR investigations, and electronic circular dichroism (ECD) calculations. All compounds were evaluated for their anti-influenza A virus and anti-influenza B virus activities against the A/PR/8/34 (H1N1), ZX1109 (H1N1, oseltamivir-resistant virus), HK68 (H3N2), and B/Florida/78/2015 strains. Compounds 3 and 4 showed significant antiviral activities against those four virus strains with EC₅₀ values ranging from 2.07 to 11.3 µM. Most notably, compound 3 exhibited potent anti-influenza B virus activity against B/Florida/78/2015 strain with EC₅₀ value of 2.27 ± 1.76 µM, versus the postive control (oseltamivir, EC₅₀ = 7.14 ± 1.94 µM).