Wild Sambucus nigra L. from north-east edge of the species range: A valuable germplasm with inhibitory capacity against SARS-CoV2 S-protein RBD and hACE2 binding in vitro.

Berries and flowers of Sambucus nigra L. tree are well known for their ability to mitigate symptoms of upper respiratory disorders related to reported antiviral properties. Industrial application and commercial cultivation of S. nigra is largely limited to a few widely grown cultivars. Restricted genetic diversity of cultivated S. nigra can be disadvantageous if new industrial applications are discovered. In this study wild S. nigra populations located on the north-east edge of the species natural range were explored by assessing genetic origin, berry and flower anti-oxidative potential, and berry rutin content. Best performing wild S. nigra extracts were selected for an assessment of previously unreported biological activity- inhibitory capacity against SARS-CoV2 S1 protein receptor binding domain (RBD) binding to recombinant human angiotensin -converting enzyme 2 (ACE2) receptor in vitro based on competitive enzyme linked immunosorbent assay (ELISA). Inter-simple sequence repeat (ISSR) marker-based genetic characterization suggested that explored wild S. nigra populations result from wild gene pool expanding northwards with admixture of historically introduced cultivated S. nigra. Average values of total phenolic content, anti-radical activity, and total flavonoids content of wild S. nigra populations did not exceed those of cv. 'Haschberg'. Concentration-dependent inhibition of ACE2-SARS-CoV2 S-protein RBD binding was demonstrated in vitro for elderberry fruits and flowers extracts (IC50 of 1.66 mg DW ml-1 and 0.532 mg DW ml-1, respectively). Wild elderberry fruit extract exhibited higher inhibitory capacity than the extract from berries of cv 'Haschberg'. This study validates the requirement for S. nigra wild germplasm bioprospecting and opens up directions for further research of new anti-SARS-CoV2 industrial applications of S. nigra.