SARS coronavirus (SARS-CoV), the causative agent of the large SARS outbreak in 2003, originated in bats. Many SARS-like coronaviruses (SL-CoVs) have been detected in bats, particularly those that reside in China, Europe, and Africa. To further understand the evolutionary relationship between SARS-CoV and its reservoirs, 334 bats were collected from Zhoushan city, Zhejiang province, China, between 2015 and 2017. PCR amplification of the conserved coronaviral protein RdRp detected coronaviruses in 26.65% of bats belonging to this region, and this number was influenced by seasonal changes. Full genomic analyses of the two new SL-CoVs from Zhoushan (ZXC21 and ZC45) showed that their genomes were 29,732 nucleotides (nt) and 29,802 nt in length, respectively, with 13 open reading frames (ORFs). These results revealed 81% shared nucleotide identity with human/civet SARS CoVs, which was more distant than that observed previously for bat SL-CoVs in China. Importantly, using pathogenic tests, we found that the virus can reproduce and cause disease in suckling rats, and further studies showed that the virus-like particles can be observed in the brains of suckling rats by electron microscopy. Thus, this study increased our understanding of the genetic diversity of the SL-CoVs carried by bats and also provided a new perspective to study the possibility of cross-species transmission of SL-CoVs using suckling rats as an animal model.

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FAK mediated tumour cell migration, invasion, survival, proliferation and regulation of tumour stem cells through its kinase-dependent enzymatic functions and kinase-independent scaffolding functions. At present, the development of FAK PROTACs has become one of the hotspots in current pharmaceutical research to solve above problems. Herein, we designed and synthesised a series of FAK-targeting PROTACs consisted of PF-562271 derivative 1 and Pomalidomide. All compounds showed significant in vitro FAK kinase inhibitory activity, the IC 50 value of the optimised PROTAC A13 was 26.4 nM. Further, A13 exhibited optimal protein degradation (85% degradation at 10 nM). Meantime, compared with PF-562271, PROTAC A13 exhibited better antiproliferative activity and anti-invasion ability in A549 cells. More, A13 had excellent plasma stability with T 1/2 >194.8 min. There are various signs that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents.

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The abnormal expression of lysine‐specific histone demethylase 1 (LSD1) is associated with different cancer types, and it is increasingly recognized as a potential therapeutic target in oncology. Here, utilizing core hopping and conformational restriction strategies, we designed and synthesized a series of coumarin analogs that were shown to be potent LSD1 inhibitors in the enzyme assay. Furthermore, several potent compounds were selected to evaluate their antiproliferative activity on A549 cells and MGC‐803 cells with high expression of LSD1. Among them, YX10 showed an anticlonogenic effect on A549 cells and MGC‐803 cells, with IC50 values of 1.52 ± 0.16 and 0.98 ± 0.18 μM, respectively. Modeling suggested that the inhibitors would bind to the active site of the protein located around the key residues of Asp555 and Lys661. Meanwhile, a preliminary druggability evaluation showed that compound YX10 showed favorable liver microsomal and moderate plasma stability and weak inhibitory activity against cytochrome P450 isoforms at 10 μM. All the results indicated that compound YX10 could represent a promising lead compound for further development.