Computational identification of potential inhibitory compounds in Indian medicinal and aromatic plant species against major pathogenicity determinants of SARS-CoV-2

SARS-CoV-2 (COVID-19) viral pandemic has been reported across 223 countries and territories. Globalized vaccination programs alongside administration of repurposed drugs will assumingly confer a stronger and longer individual specific immune protection. However, considering possible recurrence of the disease via new variants, a conveniently deliverable phytopharmaceutical drug might be the best option for COVID-19 treatment. In the current study, the efforts have been made to identify potential leads for inhalation therapy as nasal swabs have been reported to transfer viral load prominently. In that direction, 2363 Essential oil (EOs) compounds from Indian medicinal and aromatic plants were screened through docking analysis and potential candidates were shortlisted that can interfere with viral pathogenicity. The main protease (M^pro) of SARS-CoV-2 interacted closely with jatamansin (JM), 6,7-dehydroferruginol (FG) and beta-sitosterol (BS), while Papain-like Protease (PL^pro) with friedelane-3-one (F3O) and lantadene D (LD) independently. Reduced Lantadene A (LAR) exhibited preferable interaction with RNA-dependent-RNA-polymerase (RdRp) whereas Lantadene A (LA) with RdRp and spike-glycoprotein (SG-pro) both target proteins. When compared against highest binding affinity conformations of well-known inhibitors of targets, these prioritized compounds conferred superior or comparable SARS-CoV-2 protein inhibition. Additionally, promising results were noted from pharmacokinetics prediction for all shortlisted compounds. Besides, molecular dynamics simulation for 100 ns in two replicates and binding free energy analysis revealed the stability of complexes with optimum compactness. To the best of our knowledge, the current investigation is a unique initial attempt whereby EO compounds have been computationally screened, irrespective of their known medicinal properties to fight COVID-19 infection.Communicated by Ramaswamy H. Sarma.