Immunometabolism and potential targets in severe COVID-19 peripheral immune responses

In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the peripheral monocytes and lymphocytes,while these peripheral immune cells exhibit phenotypes of heterogeneously expressed interferon-stimulated genes in certain COVID-19 patients.These genes may contribute to the inhibitory response to the viral entry,translation,replication and egress.Questions remain regarding why the peripheral cytokine production is constrained,what additional roles these peripheral immune cells may play in COVID-19 pathophysiology,and which potential targets can be explored for facilitating COVID-19 therapeutics.

Novel synthetic 9-benzyloxyacridine analogue as both tyrosine kinase and topoisomerase I inhibitor

Multi-target agents against tyrosine kinases and topoisomerases are potentially useful for the effective treatment of cancers.Discovery of new multi-target scaffolds are important for developing such agents. A series of five novel acridine analogues,LXL 1-5,were synthesized and their antiproliferative activity against HepC-2 cell lines were evaluated,among which the 9-benzyloxyacridine analogue,LXL-5, showed inhibitory activity against tyrosine kinases,VEGFR-2 and Src.The results of UV-visible absorption spectra and fluorescence emission spectra,as well as DNA topoisomerase I inhibition assay, indicated topoisomerase I inhibitory activity.Our study suggested that acridine scaffold,previously shown to have no multi-target kinase and topoisomerase inhibitory activity,might be potentially developed as a multi-target inhibitor of tyrosine kinases and topoisomerase I.

Chinese Medicine Meets Conventional Medicine in Targeting COVID-19 Pathophysiology,Complications and Comorbidities

Objective: To investigate how the National Health Commission of China(NHCC)-recommended Chinese medicines(CMs) modulate the major maladjustments of coronavirus disease 2019(COVID-19),particularly the clinically observed complications and comorbidities. Methods: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology(hyperinflammations, viral replication), complications(pain, headache) and comorbidities(hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. Results: Overall,9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. Conclusion: The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.