Аннотация:
In 2019, the emergence of the seventh known coronavirus to cause severe illness in humans
triggered a global effort towards the development of new drugs and vaccines for the SARS-CoV-2
virus. These efforts are still ongoing in 2024, including the present work where we conducted a
ligand-based virtual screening of terpenes with potential anti-SARS-CoV-2 activity. We constructed a
Quantitative Structure–Activity Relationship (QSAR) model from compounds with known activity
against SARS-CoV-2 with a model accuracy of 0.71. We utilized this model to predict the activity
of a series of 217 terpenes isolated from the Fabaceae family. Four compounds, predominantly
triterpenoids from the lupane series, were subjected to an in vitro phenotypic screening in Vero CCL81 cells to assess their inhibitory activity against SARS-CoV-2. The compounds which showed high
rates of SARS-CoV-2 inhibition along with substantial cell viability underwent molecular docking
at the SARS-CoV-2 main protease, papain-like protease, spike protein and RNA-dependent RNA
polymerase. Overall, virtual screening through our QSAR model successfully identified compounds
with the highest probability of activity, as validated using the in vitro study. This confirms the
potential of the identified triterpenoids as promising candidates for anti-SARS-CoV-2 therapeutics.
