Tripeptides from Allium subhirsitum L. extracts: Pharmacokinetics properties, toxicity prediction and in silico study against SARS-CoV-2 enzymes and pro-inflammatory proteins.

Developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities is urgently needed to combat emerging human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since no available clinically antiviral drugs have been approved to eradicate COVID-19 as of the writing of this report, this study aimed to investigate bioactive short peptides from Allium subhirsutum L. (Hairy garlic) extracts identified through HR-LC/MS analysis that could potentially hinder the multiplication cycle of SARS-CoV-2 via molecular docking study. The obtained promising results showed that the peptides (Asn-Asn-Asn) possess the highest binding affinities of -8.4 kcal/mol against S protein, (His-Phe-Gln) of -9.8 kcal/mol and (Gln-His-Phe) of -9.7 kcal/mol towards hACE2, (Thr-Leu-Trp) of -10.3 kcal/mol and (Gln-Phe-Tyr) of -9.8 kcal/mol against furin. Additionally, the identified peptides show strong interactions with the targeted and pro-inflammatory ranging from -8.1 to -10.5 kcal/mol for NF-κB-inducing kinase (NIK), from -8.2 to -10 kcal/mol for phospholipase A2 (PLA2), from -8.0 to -10.7 kcal/mol for interleukin-1 receptor-associated kinase 4 (IRAK-4), and from -8.6 to -11.6 kcal/mol for the cyclooxygenase 2 (COX2) with Gln-Phe-Tyr model seems to be the most prominent. Results from pharmacophore, drug-likeness and ADMET prediction analyses clearly evidenced the usability of the peptides to be developed as an effective drug, beneficial for COVID-19 treatment.

Phytochemical Profiling of Allium subhirsutum L. Aqueous Extract with Antioxidant, Antimicrobial, Antibiofilm, and Anti-Quorum Sensing Properties: In Vitro and In Silico Studies.

The present study was the first to evaluate the phytochemical composition, antioxidant, antimicrobial, antibiofilm, and anti-quorum sensing potential of Allium subhirsutum L. (hairy garlic) aqueous extract through in vitro and in silico studies. The phytochemical profile revealed the presence of saponins, terpenes, flavonols/flavonones, flavonoids, and fatty acids, particularly with flavonoids (231 ± 0.022 mg QE/g extract), tannins (159 ± 0.006 mg TAE/g extract), and phenols (4 ± 0.004 mg GAE/g extract). Gas chromatography-mass spectrometry (GC-MS) analysis identified 15 bioactive compounds, such as 5-hydroxymethylfurfural (37.04%), methyl methanethiolsulfonate (21.33%), furfural (7.64%), beta-D-glucopyranose, 1,6-anhydro- (6.17%), 1,6-anhydro-beta-D-glucofuranose (3.6%), trisulfide, di-2-propenyl (2.70%), and diallyl disulfide (1.93%). The extract was found to be non-toxic with 50% cytotoxic concentration higher than 30,000 µg/mL. The investigation of the antioxidant activity via DPPH (2, 2-diphenyl-1-picrylhydrazyl) and FRAP (IC50 = 1 µg/mL), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); IC50 = 0.698 ± 0.107 µg/mL), and ß-carotene (IC50 = 0.811 ± 0.036 mg/mL) was assessed. Nevertheless, good antimicrobial potential against a diverse panel of microorganisms with bacteriostatic and fungistatic effect was observed. Quorum sensing inhibition effects were also assessed, and the data showed the ability of the extract to inhibit the production of violacein by the mutant C. violaceum strain in concentration-dependent manner. Similarly, the biofilm formation by all tested strains was inhibited at low concentrations. In silico pharmacokinetic and toxicological prediction indicated that, out of the sixteen identified compounds, fourteen showed promising drug ability and could be used as lead compounds for further development and drug design. Hence, these findings support the popular use of hairy garlic as a source of bioactive compounds with potential application for human health.