Abstract

Background: Severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M^pro) is an important target for drug development amidst whole variants of coronaviruses, a vital protein for the replication cycle of virus.

Objective: The main aim of this study is to discover and recognize the most effective and promising molecules against M^pro enzyme through molecular docking screening of 120 phytochemicals from six different Ayurveda medicinal plants.

Methods: The phytochemicals were downloaded from PubChem, and SARS-CoV-2 M^pro was taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed.

Results: Molecular docking analysis identified 10 phytochemicals, castalagin (-10.4 kcal/mol), wedelolactone (-8.0 kcal/mol), arjungenin (-7.7 kcal/mol), betulin (-7.7 kcal/mol), galbacin (-7.6 kcal/mol), shinpterocarpin (-7.6 kcal/mol), liquirtin (-7.4 kcal/mol), cordioside (-7.3 kcal/mol), licopyranocoumarin (-7.3 kcal/mol), and daucosterol (-7.1 kcal/mol) from different kinds of ayurvedic medicinal plants’ phytochemicals possessing greater affinity against M^pro of SARS-CoV-2. Two molecules, namely castalagin and wedelolactone, with low binding energies were the most promising. Furthermore, we carried out MD simulations for the castalagin complexes based on the docking score.

Conclusion: Molecular ADMET profile estimation showed the docked phytochemicals to be safe. The present study suggested that active phytochemicals from medicinal plants could inhibit M^pro of SARSCoV- 2.

Keywords: COVID-19, SARS-CoV-2 M^pro, molecular docking, MD simulation, Ayurveda, medicinal plants, ADMET.