Evaluation of Melongosides as Potential Inhibitors of NS2B-NS3 Activator-Protease of Dengue Virus (Serotype 2) by Using Molecular Docking and Dynamics Simulation Approach.

Dengue is a Flavivirus infection transmitted through mosquitoes of the Aedes genus, which is known to occur in over 100 countries of the world. Dengue has no available drugs for treatment; CYD-TDV is the only vaccine thus far approved for use by a few countries in the world. In the absence of drugs and a widely approved vaccine, attention has been focused on plant-derived compounds to the discovery of a potential therapeutic for DENV. The present study aimed to determine, in silico, the binding energies of the steroidal saponins, melongosides, to NS2B-NS3 activator protease of DENV-2, which plays an essential role in the viral replication. The blind molecular docking studies carried out gave binding energies (ΔG = -kcal/mol) of melongosides B, F, G, H, N, O, and P as 7.7, 8.2, 7.6, 7.8, 8.3, 8.0, and 8.0, respectively. All the melongosides interacted with the NS3 protease part of NS2B-NS3. Melongosides B, F, and N showed interactions with His51, while melongoside G interacted with Asp75 of NS3, to be noted, these are important amino acid residues in the catalytic site of the NS3 protease. However, the 200 ns molecular dynamic simulation experiment indicates significant stability of the protein-ligand interactions with the RMSD values of 2.5 Å, thus suggesting a better docking position and no disruption of the protein-ligand structure. Taken together, melongosides need further attention for more scientific studies as a DENV inhibitory agent, which if proven, in vivo and in clinical trials, can be a useful therapeutic agent against at least DENV-2.

Evaluation of antinociceptive and antihyperglycemic activities in methanol extracts of whole plants of Alternanthera philoxeroides (Mart.) Griseb. (Amaranthaceae) in mice.

The present study evaluated the antinociceptive and antihyperglycemic effects of crude methanol extract of whole plants of Alternanthera philoxeroides (Mart.) Griseb. (Amaranthaceae) in Swiss albino mice. Antin(o)Ciceptive activity was evaluated by attenuation of the number of constrictions in acetic acid-induced gastric pain, while antihyperglycemic activity was evaluated through oral glucose tolerance tests in glucose-loaded mice. Dose-dependent and significant inhibitions in the number of constrictions were seen in mice administered with extract at doses of 50, 100, 200 and 400 mg per kg body weight. At these concentrations, the numbers of constrictions were reduced, respectively, by 31.0, 32.7, 37.9 and 44.8%. In comparison, a standard antinociceptive drug, aspirin reduced the number of constrictions by 37.9 and 67.2%, when administered at doses, respectively, of 200 and 400 mg per kg body weight. The extract also exhibited dose-dependent and significant antihyperglycemic activity when administered to mice at the afore-mentioned four doses. Serum glucose concentrations were reduced, respectively, by 36.3, 58.6, 65.0 and 65.6% at the four doses administered. The results compare favorably with a standard antihyperglycemic drug, glibenclamide, which when administered at a dose of 10 mg per kg body weight reduced serum glucose level by 42.7%. Taken together, the results obtained indicate that the extract merit further scientific studies towards discovery of components, which may prove beneficial in ameliorating pain, as well as high sugar levels of diabetic patients.