Analysis of Chemical Composition and Assessment of Cytotoxic, Antimicrobial, and Antioxidant Activities of the Essential Oil of Meriandra dianthera Growing in Saudi Arabia.

The essential oil of Meriandra dianthera (Konig ex Roxb.) Benth. (Synonym: Meriandra bengalensis, Lamiaceae) collected from Saudi Arabia was studied utilizing GC and GC/MS. Forty four constituents were identified, representing 96.8% of the total oil. The M. dianthera essential oil (MDEO) was characterized by a high content of oxygenated monoterpenes (76.2%). Camphor (54.3%) was the major compound in MDEO followed by 1,8-cineole (12.2%) and camphene (10.4%). Moreover, MDEO was assessed for its cytotoxic, antimicrobial, and antioxidant activities. MDEO demonstrated an interesting cytotoxic activity against all cancer cell lines with IC50 values of 83.6 to 91.2 µg/mL, especially against MCF-7 cancer cells. Using labeling with annexin VFITC and/or propidium iodide (PI) dyes and flow cytometer analysis, the apoptosis induction was quantitatively confirmed for MCF-7 cells. The MDEO exhibited a considerable antimicrobial activity against all bacterial and fungal strains with minimum inhibitory concentration (MIC)-values of 0.07 to 1.25 mg/mL. The most sensitive microbial strain was Staphylococcus aureus (MIC: 0.07 mg/mL). Minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) values were determined one time higher than that of MIC's. Additionally, the MDEO revealed a strong activity for reducing ß-carotene bleaching with a total antioxidant value of 72.6% and significant DPPH free radical scavenging activity (78.4%) at the concentration 1000 µg/mL.

Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents.

BACKGROUND: The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic. METHODS: The main protease (Mpro) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation. RESULTS: Out of 1397 potential drugs, 157 showed considerable affinity toward Mpro. After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies -10.629 to -11.776kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (-73.800kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against Mpro. All aminoglycosides were bound to the substrate-binding site of Mpro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of Mpro. MD simulations of the Amikacin-Mpro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions. CONCLUSION: Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent.