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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions and has killed millions to date. Studies are being carried out to find therapeutic molecules that can potentially inhibit the replication of SARS-CoV-2. 3-chymotrypsin-like protease (3CL pro) involved in the polyprotein cleavage process is believed to be the key target for viral replication, and hence is an attractive target for the discovery of antiviral molecules. In the present study, we aimed to identify natural phytocompounds from Bridelia retusa as potential inhibitors of SARS-CoV-2 3CL pro (PDB ID: 6M2N) using in silico techniques. Molecular docking studies conducted with three different tools in triplicates revealed that ellagic acid (BR6) and (+)-sesamin (BR13) has better binding affinity than the co-crystal inhibitor “3WL” of 6M2N. BR6 and BR13 were found to have a high LD 50 value with good bioavailability. 3WL, BR6, and BR13 bind to the same active binding site and interacted with the HIS41-CYS145 catalytic dyad including other crucial amino acids. Molecular dynamics simulation studies revealed stability of protein–ligand complexes as evidenced from root-mean-square deviations, root-mean-square fluctuations (RMSF), protein secondary structure elements, ligand-RMSF, protein–ligand contacts, ligand torsions, and ligand properties. BR6 (−22.3064 kcal/mol) and BR13 (−19.1274 kcal/mol) showed a low binding free energy value. The Bayesian statistical model revealed BR6 and BR13 as better protease inhibitors than 3WL. Moreover, BR6 and BR13 had already been reported to elicit antiviral activities. Therefore, we conclude that ellagic acid and (+)-sesamin as natural antiviral phytocompounds with inhibitory potential against SARS-CoV-2 3CL pro. Supplementary information The online version contains supplementary material available at 10.1007/s11224-022-01959-3.

The present study was aimed to develop silybin phytosome (SIBP) and evaluate its effectiveness against cerebral ischemia-reperfusion (CIR) injury in rats. Initially, SIBP was prepared and characterized with Fourier transform-infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Drug loading and entrapment efficiency of SIBP were also calculated. High-performance liquid chromatography was used to carry out bioavailability studies of SIBP. Adult Wistar rats were divided randomly into five groups. The CIR injury was induced after 14 days of pretreatment by occlusion of bilateral common carotid arteries for 30 min followed by 4 h of reperfusion. Biochemical estimation, histopathological studies, and in silico studies were carried out. Bioavailability studies revealed that SIB concentration was increased to twofolds in SIBP-treated rats. SIBP treatment significantly increases superoxide dismutase and glutathione levels while it decreases monoaldehyde, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) levels in both the hippocampus and cortex of the SIBP-treated CIR-injured rats.Histopathological studies reveal SIBP treatment alleviates cortex cell death and arrangement of CA1 neurons in CIR-injured rats. In silico studies against proteins (TNF-α and IL-6) involved in cerebral ischemia revealed that silybin (SIB) exhibits strong binding interaction with the target proteins when compared to thalidomide which was used as the positive control. Phytosome increase SIB bioavailability and SIBP treatment showed promising results when compared to treatment with SIB only. Based on our study, we conclude that phytosome is a suitable drug delivery agent to the brain for SIB as SIBP treatment was able to provide neuroprotective action against CIR injury.

Essential oils are volatile, complex products of plants as secondary metabolites and include terpenes and their oxygenated derivatives, such as alcohols, aldehydes, esters, ketones, phenols and oxides. In recent years, out of 3000 essential oils obtained from plant origin only 300 essential oils have gained extensive attention for applications in various fields. In this review, we discuss the major biological activities associated with EOs as antimicrobial, antispasmodic, antioxidant, antiviral, anti-inflammatory, anthelmintic, insecticidal, antiparasitic, and cytotoxic agents. Different routes for delivery of essential oil along with the problems associated with essential oils like high volatility, low stability, permeability, bioavailability, poor water solubility, susceptibility to oxidation, decomposition, photosensitization and skin irritation are also highlighted. Furthermore, strategies to solve the mentioned problems are suggested by different nanoencapsulating systems. These include polymer-based nanocarriers, lipid-based nanocarriers and molecular complexes. It is believed that nanoencapsulation of essential oils will improve their therapeutic activity and delivery.