In Vitro enzymatic, antimicrobial and antiviral effects of natural products and their combinations

In this present study, in vitro antimicrobial effects, with special emphasis on sinergistic/antagonistic interactions of commercial Origanum and Eucalyptus essential oils, and their major constituents, alone or in their various combinations with standard antmicrobials were evaluated. In addition, the potential antiviral effects were tested using in vitro enzymatic assays and in silico molecular docking. Antibacterial activity and synergistic interactions of Origanum, Eucalyptus, carvacrol, thymol, ampicillin, ciprofloxacin combinations were assessed via microdilution checkerboard method, where selected most active combinations (FICI index <0.75) were further evaluated for cytotoxicity using in vitro tests. For potential antiviral activity evaluation; angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and neuraminidase (NA) assay kits were used. Also, binding, pharmacokinetic and toxicity characteristics of volatile components were assessed in silico. The major monoterpene constituents were determined by GC and GC/MS as carvacrol (62-81%) for Origanum sp., whereas as 1,8-cineol (31%) for E. globulus; and citronellal for E. citriodora (80%), respectively. In vitro enyzme test results demonstrated that O. minutiflorum, O. vulgare and E. globulus essential oils, and their major constituents inhibited ACE2, TMPRSS2 and NA enzymes, which were in correlation with in silico findings. Overall results suggests that Origanum essential oils, and carvacrol may provide better antibacterial effects when combined with antimicrobials, without toxicity. The tested Origanum and Eucalyptus essential oils with relative high enzyme inhibitions may be utilized for their antiviral potential.