The discovery of bioactive secondary metabolites from plants and marine organisms with anti-infective properties

This thesis presents the outcome of an extensive investigation into the potential of natural products as therapeutic agents against viral and bacterial pathogens. The emergence of SARS-CoV-2 (COVID-19) has resulted in a global health crisis, highlighting the urgent need for effective treatments. This work explored marine sulfated polysaccharides (MSPs) as potential antiviral agents, employing molecular docking and dynamic simulations to evaluate their interactions with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (S-protein) and human Angiotensin-Converting Enzyme-2 (ACE2). Heparin, known for preventing viral attachment to ACE2, served as a reference, and results suggest it may also block ACE2. Among the MSPs tested, nine compounds, including sulfated galactofucan and chondroitin sulfate E, exhibited promising activity against SARS-CoV-2, with several identified as novel inhibitors.In addition to antiviral efforts, the thesis evaluated the antibacterial properties of the methanolic extract of Acacia nilotica pods against the multidrug-resistant (MDR) strain Acinetobacter baumannii AB5075. Fractionation and structural characterization identified methyl gallate (MG) as the main active compound. MG displayed a minimum inhibitory concentration (MIC) of 256 μg/mL and significantly reduced bacterial loads in infected mouse lungs by approximately 1.4-log₁₀, accompanied by histopathological improvements. Although no direct target was identified for MG, its metabolite, gallic acid, is proposed to mediate its antibacterial effects with DNA gyrase as a potential target, suggesting MG might function as a prodrug.The study also investigated the antimicrobial potential of Origanum majorana L. extract against A. baumannii. The 50% methanol fraction demonstrated the highest activity (MIC=0.5 mg/mL). UPLC-HRMS identified 29 metabolites, with justicidin B emerging as a key compound targeting enoyl-ACP reductase (FabI). Molecular docking and simulations indicated that this interaction, compared to known FabI inhibitors, positions justicidin B as a promising agent against A. baumannii and other pathogens within the ESKAPE group.In conclusion, this thesis underscores the immense potential of natural products in drug discovery. Marine sulfated polysaccharides are promising candidates for antiviral strategies against SARS-CoV-2, while Acacia nilotica and Origanum majorana extracts demonstrate significant activity against MDR bacteria, particularly A. baumannii. These findings emphasize the critical role of natural products in addressing pressing global health challenges and contribute valuable insights to the development of novel therapeutic agents.