Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases.

Medicinal plants have been known to provide the essential raw material for the majority of antiviral drugs. This study demonstrated the putative inhibitory potential of curcumin, allicin, and gingerol towards cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease. The pharmacokinetic properties were predicted through the SwissADME server while the corresponding binding affinity of the selected phytocompounds towards the proteins was computed using PyRx-Python Prescription 0.8 and the binding free energy were computed based on conventional molecular dynamics using LARMD server. The ADMET properties revealed all the drugs possess drug-like properties. Curcumin has the highest binding affinities with all the selected proteases while allicin has the lowest binding affinities towards the proteases. Moreover, it was observed that curcumin exhibited the highest binding free energy of -17.90 ± 0.23,  -18.21 ± 0.25, and -9.67 ± 0.08 kcal/mol for Cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease, respectively. Based on the activities of the phytocompounds against coronavirus target proteases involved in the viral entry as evident from the results, the study, therefore, suggests that these phytocompounds could be valuable for the development of drugs useful for the prevention of coronavirus entry and replication.Communicated by Ramaswamy H. Sarma.

Molecular Mechanisms of Anti-Inflammatory Activities of the Extracts of Ocimum gratissimum and Thymus vulgaris.

BACKGROUND: A large body of literature suggests that the extracts of Ocimum gratissimum (O. gratissimum) and Thymus vulgaris (T. vulgaris) play protective roles against various inflammatory disorders. However, the possible mechanism of action with reference to the interactions of their respective phytochemical compositions with pro-inflammatory mediators as the indication of their therapeutic effects is less clear. Therefore, the immunomodulatory properties of O. gratissimum and T. vulgaris were investigated in this study. METHODS: The in vitro lipoxygenase inhibitory potentials of methanolic extracts of the selected plants were assessed through colorimetric analysis. The pharmacokinetics of some identified compounds in the botanicals were investigated via the Swiss ADME server while the molecular interactions of the compounds with lipoxygenase, IL-1, IL-6, TNF-α, IL-8, and CCL-2 were performed through molecular docking. RESULTS: The assessment of the lipoxygenase inhibition revealed the extracts could possess anti-inflammatory agents. The pharmacokinetic results of some selected compounds identified in the botanicals showed moderate toxic effects compared to indomethacin. The molecular docking study substantiated the report of the in vitro analysis as indicated in the binding score of all the selected compounds compared to indomethacin. CONCLUSION: The phytochemical components of the extracts of O. gratissimum and T. vulgaris could be effective as anti-inflammatory agents that could be explored in preventing disorders associated with excessive activities of pro-inflammatory mediators.