In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein.

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for Tinospora cordifolia, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia-a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal-using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2.

Tinospora cordifolia (Willd.) Miers: phytochemical composition, cytotoxicity, proximate analysis and their biological activities.

The present research work has been performed to evaluate the phenolic content, flavonoids content, and cytotoxicity of a multidimensional medicinal plant; Tinospora cordifolia and as well as to determine nutritive value by proximate analysis. The total phenolic and flavonoids contents of Tinospora cordifolia were found to be significantly greater in methanol extract as compared to corresponding hexane extract. Brine shrimp bioassay indicated Tinospora cordifolia is pharmacologically active. The percentage composition of different nutrition parameters namely moisture, total ash, crude fat, protein, fibre, carbohydrate, and vitamin C were assessed. The nutritive values of fresh and dried stem samples were evaluated as 156.44 Kcal/100g and 232.61 Kcal/100g respectively. From Gas column mass spectrometry analysis, it can be reported that inositol, 1-deoxy-, trans-sinapyl alcohol, n-hexadecanoic acid were present in the major amount in methanol stem extract. The findings from this study reveal Tinospora cordifolia contains an adequate amount of phenolic and flavonoids content, vital bioactive antioxidant compounds, and a good source of carbohydrates and fibers which potentially adds to the overall value of the plant.

Vitex negundo Linn.: phytochemical composition, nutritional analysis, and antioxidant and antimicrobial activity.

Vitex negundo (VN) is a widely used plant in folk medicine, namely for the treatment of jaundice, wounds, body ache, toothache, asthma, eye pain, and migraine. These effects have been increasingly attributed to its chemical composition. Here, we assessed the VN chemical and nutritional composition and biological activity, with particular emphasis on antioxidant and antimicrobial effects. VN methanol and hexane extracts revealed the presence of important phytochemical, such as terpenoids, polyphenol, steroids, saponins, phenolic compound and flavonoids. Total phenolic content of VN methanol extract from bark was 1082.473 mg/g GAE and that of leaves was 1382.984 mg/g GAE. The total flavonoids content in VN methanol extract from VN bark was 127.744 mg/g QE and that of leaves was 123.776 mg/g QE. VN methanol extract from bark exhibited high antioxidant effects (IC50=38.47 ppm). The content (%) of ash, moisture, crude fiber, crude protein and fat in VN leaves was, respectively, 7.86%, 18.35%, 6.52%, 9.687% and 6.19%. VN leaves methanol extract revealed antimicrobial activity against Bacillus subtilis and Staphylococcus aureus, with inhibition halos being, respectively, 13 mm and 14 mm, and the MBC values were found to be 1.562 mg/mL and 6.25 mg/mL, respectively. Similarly, VN bark methanol extract led to inhibition halos of 18 mm and 15 mm for B. subtilis and S. aureus, respectively, and the MBC values were found to be 2.372 mg/mL and 0.245 mg/mL. GC-MS analysis of the VN bark methanol extract revealed that monoolein was the major compounds, with an area of 0.57%. Thus, our results encourage the potential use of VN as a medicinal product, with high protein contents, and prominent antioxidant and anti-bacterial effects.