Dra. Gerli-Candia, Lorena

Since antiquity, еssential oils are considered as a source of bioactive molecules. Some of them have been shown to possess antiviral activities against various virus strains, among them SARS-CoV-2. The aim of this study is the search for compounds, among minor components extracted from different aromatic and medicinal plants collected from Algerian pharmacopeia, which may posses possible COVID-19 antiviral activities, by molecular docking in the active site of SARS-CoV-2 main protease. Materials and methods. Thus, in this study 66 compounds which are declared at traces amount by authors in the composition of the essential oils, and selected from 9 Algerian medicinal plants were docked in the active site of SARS-CoV-2 main protease as possible inhibitors of SARS-CoV-2. Results. The obtained result shows that only Cembrene constitutes the structure with the best affinity in the binding site of the enzyme with a Bioavailability Score “ABS” equal to 0.55 which confirm non Lipinski violations. However, the compound is predicted not orally bioavailable, because too lipophilic (lipophilicity: Log Po/w (XLOGP3)=6.04>+5.0) and less polar (polarity: TPSA=0.00Ų<20 Ų), and it is also predicted as not absorbed, not brain penetrant and not subject to active efflux from the CNS or to the gastrointestinal lumen. Conclusion. This result deserves to be more detailed and either confirmed or invalidated with a view to better and rational exploitation.

SARS-CoV-2 is the pandemic disease-causing agent COVID-19 with high infection rates. Despite the progress made in vaccine development, there is an urgent need for the identification of antiviral compounds that can tackle better the different phases of SARS-CoV-2. The main protease (Mpro or 3CLpro) of SARS-CoV-2 has a crucial role in viral replication and transcription. In this study, an in silico method was executed to elucidate the inhibitory potential of the synthesized 6-tert-octyl and 6-8-ditert-butyl coumarin compounds against the major protease of SARS-CoV-2 by comprehensive molecular docking and density functional theory (DFT), ADMET properties and molecular dynamics simulation approaches. Both compounds shown favorable interactions with the 3CLpro of the virus. From DFT calculations, HOMO-LUMO values and global descriptors indicated promising results for these compounds. Furthermore, molecular dynamics studies revealed that these ligand-receptor complexes remain stable during simulations and both compounds showed considerably high binding affinity to the main SARS-CoV-2 protease. The results of the study suggest that the coumarin compounds 6-tert-octyl and 6-8-ditert-butyl could be considered as promising scaffolds for the development of potential COVID-19 inhibitors after further studies.