ArticleChemistry (Weinheim an der Bergstrasse, Germany)2022
Sandacrabins - Structurally Unique Antiviral RNA Polymerase Inhibitors from a Rare Myxobacterium.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Unveiling the Taxonomic Diversity and Unprecedented Biosynthetic Treasure of the Phylum Myxococcota.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolomics andHeliyon · 2024Article
- Corrigendum: Active substances of myxobacteria against plant diseases and their action mechanisms.Frontiers in microbiology · 2024Article
- Chromosomal organization of biosynthetic gene clusters suggests plasticity of myxobacterial specialized metabolism including descriptions for nine novel species:bioRxiv : the preprint server for biology · 2023Article
- Chromosomal organization of biosynthetic gene clusters, including those of nine novel species, suggests plasticity of myxobacterial specialized metabolism.Frontiers in microbiology · 2023Article
- Active substances of myxobacteria against plant diseases and their action mechanisms.Frontiers in microbiology · 2023Review
- Thiamyxins: Structure and Biosynthesis of Myxobacterial RNA-Virus Inhibitors.Angewandte Chemie (International ed. in English) · 2022Article
- Three New Stigmatellin Derivatives Reveal Biosynthetic Insights of Its Side Chain Decoration.Molecules (Basel, Switzerland) · 2022Article
- Sandacrabins - Structurally Unique Antiviral RNA Polymerase Inhibitors from a Rare Myxobacterium.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
Corrections and comments
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Authors and funding
12 authors.
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Abstract
Structure elucidation and total synthesis of five unprecedented terpenoid-alkaloids, the sandacrabins, are reported, alongside with the first description of their producing organism Sandaracinus defensii MSr10575, which expands the Sandaracineae family by only its second member. The genome sequence of S. defensii as presented in this study was utilized to identify enzymes responsible for sandacrabin formation, whereby dimethylbenzimidazol, deriving from cobalamin biosynthesis, was identified as key intermediate. Biological activity profiling revealed that all sandacrabins except congener A exhibit potent antiviral activity against the human pathogenic coronavirus HCoV229E in the three digit nanomolar range. Investigation of the underlying mode of action discloses that the sandacrabins inhibit the SARS-CoV-2 RNA-dependent RNA polymerase complex, highlighting them as structurally distinct non-nucleoside RNA synthesis inhibitors. The observed segregation between cell toxicity at higher concentrations and viral inhibition opens the possibility for their medicinal chemistry optimization towards selective inhibitors.
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