In silico analyses of major active constituents of fingerroot (Boesenbergia rotunda) unveils inhibitory activities against SARS-CoV-2 main protease enzyme

Boesenbergia rotunda (L.) Mansf., commonly known as fingerroot is a perennial herb in the Zingiberaceae family with anticancer, anti-leptospiral, anti-inflammatory, antioxidant, antiulcer, and anti-herpes viral activities. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibitory activity of B. rotunda extract has been recently found, the active compounds contributing to this activity are yet unknown. The main protease (M(pro)) enzyme is one of the most well established therapeutic targets among coronaviruses which plays a vital role in the maturation and cleavage of polyproteins during viral replication. The current work aims to identify active phytochemical substances from B. rotunda extract that can inhibit the replication of SARS-CoV-2 by using a combined molecular docking and dynamic simulation approaches. The virtual screening experiment revealed that fifteen molecules out of twenty-three major active compounds in the plant extract have acceptable drug-like characteristics. Alpinetin, Pinocembrin, and Pinostrobin have binding energies of −7.51 kcal/mol, −7.21 kcal/mol, and −7.18 kcal/mol, respectively, and can suppress M(pro) activity. The stability of the simulated complexes of the lead compounds with the drug-receptor is demonstrated by 100-ns MD simulations. The binding free energies study utilizing molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA) show that the compounds and M(pro) enzyme have favourable thermodynamic interactions, which are majorly driven by van der Waals forces. Thus, the selected bioactive phytochemicals from B. rotunda might be used as anti-SARS-CoV-2 candidates that target the M(pro) enzyme.