ABSTRACT
The dried root of Glehnia littoralis is a traditional Chinese herbal medicine mainly used to treat lung diseases and plays an important role in fighting coronavirus disease 2019 pneumonia in China. This study focused on the key enzyme gene GlPS1 for furanocoumarin synthesis in G. littoralis. In the 35S:GlPS1 transgenic Arabidopsis study, the Arabidopsis thaliana-overexpressing GlPS1 gene was more salt-tolerant than Arabidopsis in the blank group. Metabolomics analysis showed 30 differential metabolites in Arabidopsis, which overexpressed the GlPS1 gene. Twelve coumarin compounds were significantly upregulated, and six of these coumarin compounds were not detected in the blank group. Among these differential coumarin metabolites, isopimpinellin and aesculetin have been annotated by the Kyoto Encyclopedia of Genes and Genomes and isopimpinellin was not detected in the blank group. Through structural comparison, imperatorin was formed by dehydration and condensation of zanthotoxol and a molecule of isoprenol, and the difference between them was only one isoprene. Results showed that the GlPS1 gene positively regulated the synthesis of coumarin metabolites in A. thaliana and at the same time improved the salt tolerance of A. thaliana. Supplementary Information: The online version contains supplementary material available at 10.1007/s11240-022-02427-w.
ABSTRACT
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented in human history. As a major structural protein, nucleocapsid protein (NPro) is critical to the replication of SARS-CoV-2. In this work, 17 NPro-targeting phenanthridine derivatives were rationally designed and synthesized, based on the crystal structure of NPro. Most of these compounds can interact with SARS-CoV-2 NPro tightly and inhibit the replication of SARS-CoV-2 in vitro. Compounds 12 and 16 exhibited the most potent anti-viral activities with 50% effective concentration values of 3.69 and 2.18 µM, respectively. Furthermore, site-directed mutagenesis of NPro and Surface Plasmon Resonance (SPR) assays revealed that 12 and 16 target N-terminal domain (NTD) of NPro by binding to Tyr109. This work found two potent anti-SARS-CoV-2 bioactive compounds and also indicated that SARS-CoV-2 NPro-NTD can be a target for new anti-virus agents.