Screening Active Phytochemicals of Some Ayurvedic Medicinal Plants to Identify Potential Inhibitors against SARS-CoV-2 M^pro by Computational Investigation

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 SARS-CoV-2.