Over a year on since the pandemic first emerged, the race to discover efficient antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the novel pathogen that causes coronavirus disease 2019 (COVID-19) – continues. Scientists have tried to repurpose and use existing antiviral drugs in treating SARS-CoV-2 infection, and many drugs approved by the FDA have been tested against SARS-CoV-2.
Triterpenes, their structural analogs, and their biological activities
Several trials have, in parallel, focused on the anti-SARS-CoV-2 activity of natural extracts, synthetic compounds, and immunomodulatory agents. Triterpenes are natural substances that are subject to a large number of studies due to their therapeutic, biological, and industrial value. Triterpenes and their structural analogs show various biological effects, including hypocholesterolimic, hemolytic, anti-inflammatory, immunostimulant, antiparasitic, antimicrobial, cytotoxic, and anti-ulcer effects. Additionally, they also show antiviral activities against hepatitis B and C viruses, HIV1 and 2 viruses, and Herpes simplex virus.
Oleanolic acid and maslinic acid and their antiviral activities
Oleanolic acid and maslinic acid are triterpenoids present in several plants and have several interesting biological activities, including anticancer, antimicrobial, and anti-inflammatory effects. Oleanolic acid inhibits the entry of many viruses, including HIV1, in acutely infected H9 lymphocyte cells. It has undergone several chemical modifications in recent decades to synthesize new structural analogs with favorable biological activities. These chemical modifications were mostly around the C-3 alcohol and C-17 carboxylic acid functions as well as the C12-C13 unsaturation. Various congeners of oleanolic acid have exhibited antibacterial, anticancer, anti-acetylcholinesterase, anti-inflammatory, and anti-influenza virus activities more actively than oleanolic acid.
Maslinic acid (MA) shows broad-spectrum biological activity and inhibits glycogen phosphorylases and protein tyrosine phosphatase 1B. It has drawn the attention of chemists, who used its chemical functions to produce new structural analogs, improve some of its activities, and better understand the structure-activity relationship.
Molecular docking study on structural analogs of natural maslinic and oleanolic acids to screen them against SARS-CoV-2 main protease
In a recent study published in the journal Pathogens, researchers carried out a molecular docking study for 17 structural analogs prepared from natural maslinic and oleanolic acids and screened them against SARS-CoV-2 main protease. They also experimentally validated the data by determining the half-maximal cytotoxic and inhibitory concentrations of each of the 17 compounds. The researchers investigated whether the compound with antiviral activity affected viral adsorption, replication, or viricidal effect using a plaque infectivity reduction assay.
Molecular docking is an important method of computational studies which are very promising tools in the new process of drug discovery and development as well.”
Compound 17 exhibits high affinity to SARS-CoV-2 main protease and promising antiviral activity
The study results show that the chlorinated isoxazole-linked maslinic acid or compound 17 exhibited promising antiviral activity at non-toxic, micromolar concentrations. The study also showed that compound 17 impairs the replication of SARS-CoV-2.
Most of the tested compounds showed promising affinities towards SARS-CoV-2 main protease, especially for the most active member (17),” write the researchers.
To summarize, oleanolic acid and maslinic acid, which were isolated from pomace olive oil, and their structural analogs were assessed using molecular docking to explore their expected inhibitory activities against SARS-CoV-2 main protease. Most of the compounds tested had high affinities for SARS-CoV-2 main protease, especially the most active compound 17. The authors recommend these compounds for advanced in vitro and in vivo studies in order to find an effective treatment option against the COVID-19 pandemic. According to the researchers, these compounds can even be used as combination drugs against SARS-CoV-2.
The researchers concluded a promising SAR study of the examined compounds, which could be helpful to medicinal chemists for the design and synthesis of anti-SARS-CoV-2 candidates in the future. They hope that the results will be used to guide more in vitro and in vivo studies on compound 17 to fully explore its therapeutic potential for COVID-19.