No abstract

The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.

Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) is a commonly used marine traditional Chinese medicine in the southern coastal areas of China. It has been widely used to treat rheumatoid arthritis, but its effective substances and antirheumatoid arthritis mechanism remain ambiguous. Hence, in this study, the chemical profile and absorbed ingredients of Ipomoea pes-caprae were elucidated by ultra-performance liquid chromatography-mass spectrometry. Moreover, targeted network pharmacology was used to clarify the mechanism of action of Ipomoea pes-caprae in treating rheumatoid arthritis. Finally, 23 compounds were identified in the aqueous extracts of Ipomoea pes-caprae and 12 absorbed ingredients were detected in rats' plasma. These 12 absorbed ingredients might be the essential effective substances of Ipomoea pes-caprae. The tissue distributions of 3 absorbed ingredients in rats were successfully analyzed. The targeted network pharmacological analysis results indicated that the regulation of inflammatory reaction, immune response, cell proliferation, and apoptosis were the critical mechanism of Ipomoea pes-caprae against rheumatoid arthritis. This study successfully clarified the effective substances and potential mechanisms of Ipomoea pes-caprae in treating rheumatoid arthritis. The results of this research could provide a valuable reference for further scientific research and clinical application.Article Related Abbreviations: AIA, adjuvant-induced arthritis; CFA, complete Freund's adjuvant; CYP450, cytochrome P450; FLSs, fibroblast-like synoviocytes; KEGG, Kyoto Encyclopedia of Genes and Genomes; RA, rheumatoid arthritis; TNF, tumor necrosis factor; UPLC Q-TOF-MS, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry; UPLC-TQ-MS, ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.