Revisiting the South Indian Traditional Plants against Several Targets of SARS-CoV-2 - An in silico Approach.

BACKGROUND: The south Indian Telugu states will celebrate a new year called 'Ugadi' which is a south Indian traditional festival. The ingredients used in ugadi pachadi have often also been used in food as well as traditional Ayurveda and Siddha medicinal preparations. Coronaviruses (CoVs) are a diverse family of enveloped positive-sense single-stranded RNA viruses which can infect humans and have the potential to cause large-scale outbreaks. OBJECTIVE: Considering the benefits of ugadi pachadi, we investigated the binding modes of various phytochemical constituents reported from its ingredients against five targets of SARS-CoV-2. METHODS: Flexible-ligand docking simulations were achieved through AutoDock version 1.5.6. Following 50ns of molecular dynamics simulation using GROMACS 2018.1 software and binding free energy (ΔGbind) of the protein-ligand complexes were calculated using the g_mmpbsa tool. ADME prediction was done using Qikprop of Schrodinger. RESULTS: From the molecular docking and MM/PBSA results compound Eriodictin exhibited the highest binding energy when complexed with nucleocapsid N protein (6M3M) (-6.8 kcal/mol, - 82.46 kJ/mol), bound SARS-CoV-2-hACE2 complex (6M0J) (-7.4 kcal/mol, -71.10 kJ/mol) and Mpro (6XR3) (-8.6 kcal/mol, -140.21 kJ/mol). Van der Waal and electrostatic energy terms highly favored total free energy binding. CONCLUSION: The compounds Eriodictin, Vitexin, Cycloart-3, 24, 27-triol, Agigenin, Mangiferin, Mangiferolic acid, Schaftoside, 27-Hydroxymangiferonic acid, Quercetin, Azadirachtol, Cubebin, Isomangiferin, Isoquercitrin, Malicarpin, Orientin and procyanidin dimer exhibited satisfactory binding energy values when compared with standard molecules. The further iterative optimization of high-ranked compounds following validation by in vitro and in vivo techniques assists in discovering therapeutic anti-SARS-CoV-2 molecules.

Neuroprotective effect of Clerodendrum serratum Linn. leaves extract against acute restraint stress-induced depressive-like behavioral symptoms in adult mice.

OBJECTIVE: The objective of this study was to study the effect of ethanol extract of Clerodendrum serratum (EECS) Linn. on acute restraint stress (ARS)-induced depressive-like behavior and biochemical alterations in mice. MATERIALS AND METHODS: Ethyl acetate and n-butanol fractions of EECS were analytically characterized for the flavonoid components, apigenin (API) and luteolin (LUT) by reverse-phase high-performance liquid chromatography. Behavioral tests, namely, forced-swim test and tail-suspension test were performed for assessing antidepressant-like effect and anxiolytic activity in mice. Oxidative stress parameters and biochemical alterations in mice brain tissue were also performed. STATISTICAL ANALYSIS: Expression of data was done as mean ± standard error of mean. The normally distributed data were subjected to two-way ANOVA followed by Dunnett's test. P < 0.05 was considered statistically significant. RESULTS: The study showed that flavonoids, API and LUT were present in ethyl acetate and n-butanol fractions of EECS, which significantly reversed ARS-induced depressive-like behavior without affecting locomotion. EECS also attenuated oxidative damage caused by ARS. The level of norepinephrine and 5-hydroxytryptamine was also significantly restored by pretreatment with EECS for 7 days. CONCLUSION: EECS significantly alleviated ARS-induced depressive-like behavior without affecting locomotion.