Background: The recent outbreak of Coronavirus SARS-CoV-2 (Covid-19), which has
rapidly spread around the world in about three months with tens of thousands of deaths recorded so
far is a global concern. An urgent need for potential therapeutic intervention is of necessity. Mpro is
an attractive druggable target for the development of anti-COVID-19 drug development.
Methods: Compounds previously characterized by Melissa officinalis were queried against the
main protease of coronavirus SARS-CoV-2 using a computational approach.
Results: Melitric acid A and salvanolic acid A had higher affinity than lopinavir and ivermectin using
both AutodockVina and XP docking algorithms. The computational approach was employed in
the generation of the QSAR model using automated QSAR, and in the docking of ligands from
Melissa officinalis with SARS-CoV-2 Mpro inhibitors. The best model obtained was KPLS_Radial_
28 (R2 = 0.8548 and Q2=0.6474, which was used in predicting the bioactivity of the lead compounds.
Molecular mechanics based MM-GBSA confirmed salvanolic acid A as the compound
with the highest free energy and predicted bioactivity of 4.777; it interacted with His-41 of the catalytic
dyad (Cys145-His41) of SARS-CoV-2 main protease (Mpro), as this may hinder the cutting of
inactive viral protein into active ones capable of replication.
Conclusion: Salvanolic acid A can be further evaluated as a potential Mpro inhibitor.