Standardized <i>Eucalyptus maculata</i> (<i>Corymbia maculata</i>) Resin Extract: Metabolomic Profiling, In Vitro and In Silico Study of Anti‐HSV Activity

Abstract

Recent episodes of viral pandemics have led to a quest for new drugs to act on emerging targets. Most challenging viruses are only mutants of already known viruses. Here comes the role of metabolomics in investigating natural secondary metabolites as sustainable antiviral drug candidates. Resins are natural plant products having the advantage of being concentrated and consisting of precious terpenoids, phenolics, and flavonoids, known for their anti-pathogen activity. This study aimed at investigation of the major phytoconstituents in the Eucalyptus maculata (EM) resin using high resolution liquid chromatography-mass spectrometry (LC-MS/MS) and investigating its antiviral potential. In vitro screening of the standardized EM antiviral activity was performed. High resolution LC-MS/MS analysis was done for the extract followed by investigation of the possible active metabolites through molecular docking techniques against two viral protein targets; herpes simplex virus glycoprotein D (HSV gD) and B- and T-lymphocyte attenuator/herpes virus entry mediator complex. The evaluation in negative and positive modes identified 29 substances and revealed the prevalence of coumaryl and galloyl derivatives, in addition to kaempferol and aromadendrin derivatives. Antiviral in vitro screening led to the conclusion of the promising effect of the resin against HSV that was further confirmed through molecular docking. EM resin represents a future sustainable drug discovery and should be further investigated as an antiviral agent.