Phytochemical Mining of Potential SARS-CoV-2 Main Protease Inhibitors from Blumea balsamifera (L.) DC.

Abstract

Blumea balsamifera (L.) DC is a medicinal plant widely used against various ailments throughout Asian and African cultures. The reported efficacy of B. balsamifera and its phytochemicals against respiratory disorders suggests that it can be a potential therapeutic against the coronavirus disease 2019 (COVID-19), which is also a respiratory disease. This potential was demonstrated through an in silico assessment utilizing B. balsamifera phytochemicals and targeting the severe acute respiratory syndrome–coronavirus-2 main protease (SARS-CoV-2 Mpro), an enzyme that plays an important role in the infection process by SARS-CoV-2. The general strategy implemented was termed phytochemical mining in tandem with virtual screening (PM-VS). Data gathering of B. balsamifera phytochemicals reported in the literature was first conducted (PM stage) followed by VS through automated molecular docking of multiple ligands. The present study obtained the most comprehensive phytochemical record and organization of B. balsamifera phytochemicals (a total of 331). Surprisingly, 113 of the unique phytochemicals were promising SARS-CoV-2 Mpro inhibitors, of which 12 were re-discovered antiviral drugs from the plant. The promising inhibitors also reveal interesting in silico drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Further analysis of the promising phytochemicals and their interactions with SARS-CoV-2 Mpro hints at the phenylpropanoid moiety (Ph-C3-) as a potential pharmacophore of the target enzyme. This study illustrated the utility of PM-VS in the preliminary stages of drug discovery and development; however, further studies (e.g. exhaustive VS and definitive “ex silico” experiments) are needed to confirm the present finding.