Arylnaphthalene Lignans with Anti-SARS-CoV-2 and Antiproliferative Activities from the Underground Organs of Linum austriacum and Linum perenne .

Diphyllin () and justicidin B () are arylnaphthalene lignans with antiviral and antiproliferative effects. Compound is also known as an effective inhibitor of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To evaluate the antiviral and cytotoxic potency of both lignans in SARS-CoV-2 -infected cells and various cancer cell lines, respectively, and were isolated from the underground organs of and . Two previously undescribed arylnaphthalene lignans, denominated linadiacin A and B ( and ), were also isolated and identified. In acidic media, was converted by a two-step reaction into via the intermediate . Optimum acid treatment conditions were determined to isolate lignans by one-step preparative high-performance liquid chromatography (HPLC). The results of the conversion, HPLC-tandem mass spectrometry, nuclear magnetic resonance spectroscopy, and molecular modeling studies allowed complete structure analysis. Compounds and were the most effective against SARS-CoV-2 with a 3-log reduction in the viral copy number at a 12.5 μM concentration. Ten human cancer cell lines showed sensitivity to at least one of the isolated lignans.