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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., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality in the world. The morbidity and mortality of HCC are increasing every year. Liver cancer is a serious threat to public health in China and the death rate of patients with liver cancer in China is the highest in the world. Beyond surgery, chemotherapy and radiotherapy, immunotherapy is an emerging treatment for cancer, which could control and kill tumor cells by relieving the inhibitory status of immune cells in the tumor microenvironment and activating the immune function of the body. Immune checkpoint inhibitors, adoptive immunotherapy and tumor vaccine are the major treatments of immunotherapy. Compared with traditional therapy methods, immunotherapy could enhance immune function, delay tumor progression, prolong the survival time of patients, and becomes a hotspot in the basic and clinical cancer research. This article reviews the research progress of immunotherapy for liver cancer.