We report structure elucidation and total synthesis of five unprecedented terpenoid-alkaloids, the sandacrabins, alongside with the very first description of their creating organism Sandaracinus defensii MSr10575, which expands the Sandaracineae loved ones by only its second member. The genome sequence of S. defensii as presented within this study was utilized to identify enzymes responsible for sandacrabin formation, whereby dimethylbenzimidazol, deriving from cobalamin biosynthesis, was identified as crucial intermediate. Biological activity profiling revealed that all sandacrabins except congener A exhibit potent antiviral activity against the human pathogenic coronavirus HCoV229E within the 3 digit nanomolar range. Investigation on the underlying mode of action discloses that the sandacrabins inhibit the SARS-CoV-2 RNA-dependent RNA polymerase complicated, highlighting them as structurally distinct non-nucleoside RNA synthesis inhibitors. The observed segregation among cell toxicity at greater concentrations and viral inhibition represents an excellent beginning point for their medicinal chemistry optimization towards selective inhibitors. Iridium(III) acetate trihydrate uses Buy1-Methyl-1H-indazol-5-ol PMID:23008002