The emergence of multidrug-resistant Mycobacterium tuberculosis (MTB) has become a major problem in treating tuberculosis (TB) and shows the need to develop new and efficient drugs for better TB control. This study aimed to use in silico techniques to discover potential inhibitors to the Enoyl-[acyl-carrier-protein] reductase (InhA), which controls mycobacterial cell wall construction. Initially, 391 quercetin analogs present in the KNApSAck_3D database were selected, filters were sequentially applied by docking-based virtual screening. After recategorizing the variables (bond energy prediction and molecular interaction, including hydrogen bond and hydrophobic bond), compounds C00013874, C00006532, and C00013887 were selected as hit ligands. These compounds showed great hydrophobic contributions, and for each hit ligand, 100 ns of molecular dynamic simulations were performed, and the binding free energy was calculated. C00013874 demonstrated the greatest capacity for the InhA enzyme inhibition with ΔGbind = −148.651 kcal/mol compare to NAD (native ligand) presented a ΔGbind = −87.570 kcal/mol. These data are preliminary studies and might be a suitable candidate for further experimental analysis.

Human pancreatic α-amylase inhibition is currently a promising therapeutic target against type 2 diabetes (DMT2) because it can reduce aggressive digestion of carbohydrates into absorbable monosaccharides. In Indonesia, medicinal plants, e.g. Morinda citrifolia fruit, have been empirically utilized as a blood-sugar reducer, however, the inhibitory activity of compounds in this plant against human pancreatic α-amylase is still limited or none. Therefore, this study aimed to test the interaction of 7 compounds (americanin, asperulosidic acid, damnacanthal, quercetin, rutin, scopoletin, and ursolic acid) contained in noni fruit against human pancreatic α-amylase by molecular docking and molecular dynamics and compared their binding modes with that of acarbose. Results of the molecular docking simulation indicated that the ursolic acid compound possesses the best binding energy (-8.58 kcal/mol) and comparable to that of acarbose (-8.59 kcal/mol). The molecular dynamics study at 100 ns simulation, the values of RMSD, RMSF, the radius of gyration (Rg), the solvent-accessible surface area (SASA), principal component analysis (PCA), and MM-PBSA binding free energy were stable and identical to those of acarbose. It could be concluded that ursolic acid might be potential in inhibiting human pancreatic α-amylase, thus, potential to be developed as an anti-DMT2 drug candidate. Communicated by Ramaswamy H. Sarma

The EGFR-C797S resistance mutation to third-generation drugs has been overcome by fourth-generation inhibitors, allosteric inhibitors, namely EAI045 and has reached phase 3 clinical trials, so the Allosteric Site is currently an attractive target for development. In this study, researchers are interested in knowing the activity of metabolite compounds from marine natural ingredients Clathria Sp. against the Allosteric Site of EGFR computationally. The methods used include molecular docking using Autodock4 software and Molecular Dynamics simulation performed using GROMACS software. The research began with the preparation of metabolite samples from Clathria Sp. through the KnapSack database site and the preparation of EGFR receptors that have been complexed with allosteric inhibitors, namely proteins with PDB code 5D41. Each compound was docked to the Allosteric Site of the natural ligand and then molecular dynamics simulations were performed on the compound with the best docking energy compared to the natural ligand. From the docking results, the Clathrin_A compound showed the lowest binding energy compared to other metabolites, and the value was close to the natural ligand. Then from the molecular dynamics results, the clathrin_A compound shows good stability and resembles the natural ligand, which is analyzed through RMSD, RMSF, SASA, Rg, and PCA, and shows the binding free energy from MMPBSA analysis which is close to the natural ligand. It can be concluded, Clathrin_A compound has potential as an allosteric inhibitor.

The target for COVID-19 has been successfully crystallized along with its inhibitor, named SARS-CoV-2 main protease, making it easier for drug discovery and development. Sponge (Clathria Sp.) is a marine species that can be found in Indonesia and has a unique chemical structure that is still rarely explored in its properties. Therefore, this study aims to examined the potential of marine natural products from sponge (Clathria Sp.) as SARS-CoV-2 main protease inhibitor using in silico method. The ligand structures were obtained from the Knapsack database and the protein structure obtained from the RCSB site with the PDB code: 6LU7. The molecular docking method was validated by re-docked the native ligand and calculated the RMSD value. The compounds contained in Sponge were docked into the active site of the protein based on the validated methods. Afterward, the molecular dynamics were performed for 100 ns simulation, then analyzed its system complex stability. The RMSD 1.329 Å was obtained by re-docked of native ligand which indicates that the docking method was valid. Molecular docking of the ligands showed mirabilin_G has binding energy −7.38 kcal/mol, compared to the native ligand N3 inhibitor that is −7.30 kcal/mol, and the ligand showed good stability from molecular dynamics simulation indicated by RMSD, RMSF and MM-PBSA binding free energy similar to the inhibitor during 100 ns simulation. Its indicated the potential of the compounds contained in the sponge as inhibitor of SARS-CoV-2 main protease. Communicated by Ramaswamy H. Sarma

Previous in vivo studies of Morinda citrifolia (Rubiaceae) reported that the extract inhibited α-amylase and reduced blood glucose levels in streptozotocin-induced diabetes mice. Moreover, molecular docking studies confirmed that ursolic acid and sterol compounds contained in the fruit interacted with important residues in the binding site of α-amylase and α-glucosidase. Our work aimed to study the complex stability of stigmasterol (which has been isolated from the M. citrifolia fruit for the first time) and beta-sitosterol towards α-amylase and α-glucosidase by employing molecular dynamics simulation on GROMACS 2016.3 embedded with the AMBER99SB-ILDN force field. The simulation was carried out for 100 ns at 310 ^oK. Based on the RMSD and RMSF graphs, the complexes of stigmasterol/α-amylase and stigmasterol/α-glucosidase are more stable compared to acarbose, the known inhibitor of both enzymes. Moreover, beta-sitosterol indicates a better stability complex with α-glucosidase compared to that of acarbose. Interestingly, the affinity of stigmasterol and beta-sitosterol to both enzymes, in terms of the total binding energy, is stronger than that of acarbose. Taken together, stigmasterol and beta-sitosterol in M. citrifolia fruit may have the potency to be developed as α-amylase and α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.