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Nat Commun . Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Feb 20;15(1):1537.
doi: 10.1038/s41467-024-45690-5. Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery

Liang Leng[SUP] #[/SUP][SUP] 1 [/SUP], Zhichao Xu[SUP] #[/SUP][SUP] 2 [/SUP], Bixia Hong[SUP] #[/SUP][SUP] 3 [/SUP], Binbin Zhao[SUP] #[/SUP][SUP] 4 [/SUP], Ya Tian[SUP] 2 [/SUP], Can Wang[SUP] 1 [/SUP], Lulu Yang[SUP] 1 [/SUP], Zhongmei Zou[SUP] 5 [/SUP], Lingyu Li[SUP] 5 [/SUP], Ke Liu[SUP] 3 [/SUP], Wanjun Peng[SUP] 4 [/SUP], Jiangning Liu[SUP] 4 [/SUP], Zhoujie An[SUP] 2 [/SUP], Yalin Wang[SUP] 2 [/SUP], Baozhong Duan[SUP] 6 [/SUP], Zhigang Hu[SUP] 7 [/SUP], Chuan Zheng[SUP] 8 [/SUP], Sanyin Zhang[SUP] 1 [/SUP], Xiaodong Li[SUP] 9 [/SUP], Maochen Li[SUP] 3 [/SUP], Zhaoyu Liu[SUP] 1 [/SUP], Zenghao Bi[SUP] 1 [/SUP], Tianxing He[SUP] 1 [/SUP], Baimei Liu[SUP] 1 [/SUP], Huahao Fan[SUP] 10 [/SUP], Chi Song[SUP] 11 [/SUP], Yigang Tong[SUP] 12 [/SUP], Shilin Chen[SUP] 13 [/SUP]



Affiliations
Abstract

Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.


 
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