In vitro and in silico antiviral activity of GC–MS-identified metabolites from three South African medicinal plants against H1N1 and SARS-CoV-2

Abstract

Influenza A virus subtype H1N1 (H1N1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can both infect the respiratory tract and cause symptoms such as fever, cough, and shortness of breath. Medicinal plants offer an alternative treatment strategy, as they can provide relief against these respiratory-related viruses. The present study aimed to evaluate the antiviral activity and molecular modelling of metabolites from Eucalyptus globulus Labill., Schinus molle L., and Searsia lancea (L.f) F.A.Barkley. The detection and identification of volatile phytoconstituents in the extracts were performed by GC-MS analysis. The samples were further assessed through the in vitro activity screening and followed by molecular modelling-mediated prediction of bioactive constituents. Volatile compounds were identified in hexane extracts, with hydrocarbons accounting for the highest peak percentage across all three plant samples. Hexane extracts from all three plants demonstrated inhibitory activity, varying in potency, with E. globulus and S. molle extracts being highly potent (IC50 values < 100 μg/mL) against PLpro from SARS-CoV-2. Accordingly, the in silico study identified geranylgeranyl acetate from S. molle and 1-tetracosanol from both E. globulus and S. molle as potential inhibitors of the SARS-CoV-2 protease (PDB: 7MB1). Molecular dynamics revealed that they formed stable complexes with the SARS-CoV-2 protease and interacted with key active-site amino acid residues, including the catalytic site residues His41 and Cys145. The results of this study highlight the need to assess the efficacy of geranylgeranyl acetate and 1-tetracosanol against the SARS-CoV-2 protease in pharmacological in vitro and in vivo studies.