Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation. 相似文献
Canine mammary tumors (CMTs) are one of the most common malignancies in dogs and are associated with significant mortality. Serum tumor markers and non-coding microRNAs have gained widespread popularity in human oncology studies. The present study has two aims, first one is to investigate the miR-21 expression compared with changes in serum tumor markers (CEA and CA15-3) in CMT. The second aim is to detect the immunohistochemistry markers as vimentin, P63, and -SMA in CMT.
Methods
This study enrolled 17 female dogs: 10 with mammary tumors and seven controls without tumors. Blood samples were collected to measure miR-21, CEA, and CA 15-3, and histological samples were prepared for histological grading and immunohistochemistry.
Results
CA 15-3 was elevated in all animals, whereas CEA levels showed no change compared with controls. miR-21 was upregulated 12.84-fold in animals with CMT. The most frequently recorded CMT was the mixed type. Myoepithelial cells were identified by P63 immunoreactivity, but not SMA. High expression of miR-21 was observed with positive vimentin immunoreactivity, indicating the mesenchymal origin of the tumor cells.
Conclusion
The present study showed that miR-21 was elevated to a greater extent than CA 15-3 (12.84-fold vs. threefold). Tumors that was positive for vimentin immunoreactivity was also associated with an elevation in the levels of miR-21, showing that miR-21 is released from mesenchymal cells. These findings support the hypothesis that miR-21 may be a more sensitive, noninvasive indicator for CMT.
Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by 1H NMR. Ten known compounds, including angucycline, diketopiperazine and β-carboline derivatives 1–10, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine (12) and 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a). When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes. 相似文献