In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) commenced in Wuhan, China and affected around 210 countries and territories in a matter of weeks. It has a phylogenetic similarity to SARS-CoV and it was named coronavirus 2 (SARS-CoV-2) and caused severe acute respiratory syndrome that could lead to death. One of the promising therapeutic strategies for virus infection is the search for enzyme inhibitors among natural compounds using molecular docking in order to obtain products with minimal side effects. COVID-19 virus main protease plays a vital role in mediating viral transcription and replication, introducing it as an attractive antiviral agent target. Metabolic profiling of the aqueous extract of Salvadora persica L. (Salvadoraceae) aerial parts dereplicated eleven known flavonol glycosides using LC-HRESIMS. All the annotated flavonoids exhibited significant binding stability at the N3 binding site to different degrees, except isorhamnetin-3-O-β-D-glucopyranoside, when compared with the currently used COVID-19 main protease inhibitor, darunavir. Structural similarity between the identified flavonoids enabled the study of the relationship between their structure and interactions with the receptor in the N3 binding site of the COVID-19 main protease. The results indicate that the basic flavonol nucleus possesses activity itself. Moreover, the presence of a rutinose moiety at the 3 position of ring C and absence of an O-methyl group in ring B of the flavonol structure could increase the binding stability. This study provides a scientific basis for the health benefits of the regular use of S. persica as it leaches bioactive flavonoids in the aqueous saliva.

Legume sprouts are a fresh nutritive source of phytochemicals of increasing attention worldwide owing to their many health benefits. Nuclear magnetic resonance (NMR) was utilized for the metabolite fingerprinting of 4 major legume sprouts, belonging to family Fabaceae, to be exploited for quality control purposes. Thirty-two metabolites were identified belonging to different classes, i.e., fatty acids, sugars, amino acids, nucleobases, organic acids, sterols, alkaloids, and isoflavonoids. Quantitative NMR was employed for assessing the major identified metabolite levels and multivariate data analysis was utilized to assess metabolome heterogeneity among sprout samples. Isoflavones were detected exclusively in Cicer sprouts, whereas Trigonella was characterized by 4-hydroxyisoleucine. Vicia sprouts were distinguished from other legume sprouts by the presence of L-Dopa versus acetate abundance in Lens. A common alkaloid in all sprouts was trigonelline, detected at 8–25 µg/mg, suggesting its potential role in legume seeds’ germination. Trigonelline was found at highest levels in Trigonella sprouts. The aromatic NMR region data (δ 11.0–5.0 ppm) provided a better classification power than the full range (δ 11.0–0.0 ppm) as sprout variations mostly originated from secondary metabolites, which can serve as chemotaxonomic markers.

Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC₅₀ values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.

Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC–HRESIMS. The identified metabolites (1–34) belonged to different chemical classes, including iridoids, flavones, phenyl ethanoids, and lignans. A phytochemical investigation of P. odorata bark afforded one new tetrahydrofurofuran lignan, 4β-hydroxyasarinin 35, along with fourteen known compounds. The structure of the new compound was confirmed using extensive 1D and 2D NMR, and HRESIMS analyses. A cytotoxic investigation of compounds 35–38 against the HL-60, HT-29, and MCF-7 cancer cell lines, using the MTT assay showed that compound 35 had cytotoxic effects against HL-60 and MCF-7 with IC₅₀ values of 2.7 and 4.2 µg/mL, respectively. A pharmacophore map of compounds 35 showed two hydrogen bond acceptor (HBA) aligning the phenoxy oxygen atoms of benzodioxole moieties, two aromatic ring features vectored on the two phenyl rings, one hydrogen bond donor (HBD) feature aligning the central hydroxyl group and thirteen exclusion spheres which limit the boundaries of sterically inaccessible regions of the target’s active site.

Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant extract and its liposomal formulation were shown to inhibit SARS-CoV-2 in an in vitro A549 cell line culture and a RT-PCR test almost as well as the FDA-approved anti-COVID-19 agent, remdesivir. Encapsulation within liposomal formulation led to a highly significant increase in the percentage of inhibition of viral replication from 38.09 ± 0.83 to 85.56 ± 1.12% in a flavonoid mixture and its liposomal preparation, respectively, and this figure approached that obtained for remdesivir (91.20 ± 1.71%). Preliminary tests were also performed, including a total flavonoid assay, a molecular docking study, a 3CL-protease inhibition assay and a cytotoxicity study. It was worthy to find a cheap, readily available, safe natural source for promising anti-SARS-CoV-2 agents, that leak their phytochemicals into the aqueous saliva during regular use as a brushing agent.

Silybum marianum (L.) Gaertn. (Asteraceae) was hydroponically cultured using a nutrient film technique system. Silibinin, isosilibinin and silychristin were detected in the fruits of the cultured plants. The effect of salicylic acid on the improvement of flavonolignans production by the fruits of the hydroponically cultured S. marianum was investigated. Salicylic acid was added to the nutrient solution at different concentrations (100, 200 and 400 µM) and the mature fruits of the plant were collected five days after elicitor addition. The fruits were then analyzed for their total flavonolignans contents and individual components using quantitative proton nuclear magnetic resonance spectroscopy (qHNMR) and high-performance liquid chromatography (HPLC). The results showed that elicitation with salicylic acid at 200 µM for five days increased production of total flavonolignans (1.7-fold by qHNMR and 1.6-fold by HPLC) higher than the control cultures and (1.4-fold by qHNMR and 1.1-fold by HPLC) higher than the cultivated plants. Silychristin was the major flavonolignan produced by the cultured plant. Elicitation by 200 µM salicylic acid increased silychristin production (1.6-fold by qHNMR and HPLC) higher than the control cultures and (1.3-fold by qHNMR and 1.0-fold by HPLC) higher than the cultivated plants. The present study provides a chance to improve secondary metabolite yield, serves as a useful tool for studying the biosynthesis of these medicinally valuable compounds and its regulation in plant and spots more light on hydroponic system as an important agricultural technique.