Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy.

Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main protease (Mpro) and the receptor binding domain (RBD) using molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. To this end, thirty-five naturally occurring phenolics were identified and subjected to molecular docking simulation against the proteins. The results showed the compounds including rosmarinic acid, cynarine, and chlorogenic acid among many others possessed high binding affinities for both proteins as evident from their docking scores, with some possessing lower docking scores compared to the standard compound (Remdesivir). Further subjection of the hit compounds to drug-likeness, pharmacokinetics, and toxicity profiling revealed chlorogenic acid, rosmarinic acid, and chicoric acid as the compounds with desirable profiles and toxicity properties, while the study of their electronic properties via density functional theory calculations revealed rosmarinic acid as the most reactive and least stable among the sets of lead compounds that were identified in the study. Molecular dynamics simulation of the complexes formed after docking revealed the stability of the complexes. Ultimately, further experimental procedures are needed to validate the findings of this study.

Microscopic visualization of the antibiofilm potential of essential oils against Staphylococcus aureus and Klebsiella pneumoniae.

Biofilms are known to pose great risks in clinical settings, drinking water systems, and food industries as they show considerable resistance to various environmental stresses. This study investigates the antibiofilm potential of different essential oils against the test organisms Staphylococcus aureus (ATCC 25923) and Klebsiella pneumoniae (ATCC 13883). Moreover, different stages of biofilm formation were also assessed using light microscopic assays. For determining the antibiofilm activity, a total of five essential oils namely cinnamon (Cinnamomum Verum), tea tree (Melaleuca alternifolia), lavender (Lavandula), peppermint (Mentha piperita), and lemongrass (Cymbopogon citratus) were tested for their ability to inhibit the initial attachment of microbial cells as well as the eradication of mature biofilm using the microtitre plate assay. For both the test strains (S. aureus and K. pneumoniae) the concentration of 30 µl/100 µl of cinnamon oil exhibited the highest antibiofilm activity followed by the activity of peppermint oil at the same concentration. These results were further validated by employing the light microscopy assay for observing the antibiofilm potential of cinnamon and peppermint essential oils.