Coronavirus disease 2019 (COVID‐19) is an infectious respiratory disease caused by a new strain of the coronavirus. There is limited data on the pathogenesis and the cellular responses of COVID‐19. In this study, we aimed to determine the variation of metabolites between healthy control and COVID‐19 via the untargeted metabolomics method. Serum samples were obtained from 44 COVID‐19 patients and 41 healthy controls. Untargeted metabolomics analyses were performed by the LC/Q‐TOF/MS (liquid chromatography quadrupole time‐of‐flight mass spectrometry) method. Data acquisition, classification, and identification were achieved by the METLIN database and XCMS. Significant differences were determined between patients and healthy controls in terms of purine, glutamine, leukotriene D4 (LTD4), and glutathione metabolisms. Downregulations were determined in R‐S lactoglutathione and glutamine. Upregulations were detected in hypoxanthine, inosine, and LTD4. Identified metabolites indicate roles for purine, glutamine, LTD4, and glutathione metabolisms in the pathogenesis of the COVID‐19. The use of selective leukotriene D4 receptor antagonists, targeting purinergic signaling as a therapeutic approach and glutamine supplementation may decrease the severity and mortality of COVID‐19.

With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

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Introduction Numerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS‐CoV‐2. Objective The main objective of our study was to determine artemisinin content by liquid chromatography electrospray ionisation tandem mass spectrometry (LC‐ESI‐MS/MS), to investigate the in vitro biological activity of artemisinin from the A. annua plants grown in Turkey with various extracted methods, to elaborate in silico activity against SARS‐CoV‐2 using molecular modelling. Methodology Twenty‐one different extractions were applied. Direct and sequential extractions studies were compared with ultrasonic assisted maceration, Soxhlet, and ultra‐rapid determined artemisinin active molecules by LC‐ESI‐MS/MS methods. The inhibition of spike protein and main protease (3CL) enzyme activity of SARS‐CoV‐2 virus was assessed by time resolved fluorescence energy transfer (TR‐FRET) assay. Results Artemisinin content in the range 0.062–0.066%. Artemisinin showed significant inhibition of 3CL protease activity but not Spike/ACE‐2 binding. The 50% effective concentration (EC50) of artemisinin against SARS‐CoV‐2 Spike pseudovirus was found greater than 50 μM (EC45) in HEK293T cell line whereas the cell viability was 94% of the control (P < 0.01). The immunosuppressive effects of artemisinin on TNF‐α production on both pseudovirus and lipopolysaccharide (LPS)‐induced THP‐1 cells were found significant in a dose dependent manner. Conclusion Further studies of these extracts for COVID‐19 treatment will shed light to seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.