Investigation of Rosemary Active Ingredients as COVID-19 Inhibitors: Molecular Docking and DFT

Abstract

Rosemary is an important type of the natural Lamiaceae plant family with several medicinal properties, rendering it as a prospective inhibitor for the new SARS-CoV-2 virus. Its SARS-CoV-2 inhibition properties has not yet been reported. In this study the inhibition efficacy of rosemary against SARS-CoV-2 has been demonstrated using molecular docking along with systematic density-functional-theory (DFT) calculations. The estimated DFT data have shown that the dipole moment of rosemary active ingredient was in the range of 4.29-1.68 with the highest value attained by the carnosic acid. The high dipole moment for the carnosic acid may indicate its appropriate binding affinity pose within a specific virus target receptor. Moreover, the structural complexity for the carnosic acid gave rise to its highest calculated polarizability of 225.5 Bohr3 compared to the rest of the rosemary ingredients. Remarkably, the carnosic acid active ingredient has the least energy gap between the frontier orbitals (highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)) of ~ 5.43 eV, with several hydrophilic sites for interactions, further enabling its binding with the virus receptors. Interestingly, and as anticipated from DFT results, molecular docking calculations showed that carnosic acid had the least binding energy (−6.9 kcal/mol) and, hence, can be regarded as a prospective inhibitor to SARS-CoV-2 main protease (Mpro). It binds to both Mpro catalytic dyads (Cys-145 and His-41) with hydrogen bond and π-interaction. This carnosic acid ligand binding quality was comparable to renowned SARS-CoV-2 drugs, hydroxychloroquine and favipiravir, having binding affinities of −6.1 and −5.1 kcal/mol, respectively.