Nature communications · 2024
Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Leng Liang, Xu Zhichao, Hong Bixia, Zhao Binbin, Tian Ya, Wang Can, Yang Lulu, Zou Zhongmei, Li Lingyu, Liu Ke, Peng Wanjun, Liu Jiangning, An Zhoujie, Wang Yalin, Duan Baozhong, Hu Zhigang, Zheng Chuan, Zhang Sanyin, Li Xiaodong, Li Maochen, Liu Zhaoyu, Bi Zenghao, He Tianxing, Liu Baimei, Fan Huahao, Song Chi, Tong Yigang, Chen Shilin
Аннотация
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.