This study is carried out to find novel active drug candidates which can effectively bind to key residues of main protease (Mpro) of SARS-CoV-2. We performed molecular docking of fifty-seven (57) ligands from two classes: vanillylacetone and its derivatives and beta-hydroxy ketone derivatives against Mpro of SARS-CoV-2. We also docked three antiviral drugs as reference/benchmark drugs including remdesivir (RDV), chloroquine (CQ), and hydroxychloroquine (HCQ) against Mpro for comparison of inhibition tendencies of selected ligands. Binding energies of our reference drugs are as: CQ = -5.1 kcal mol-1 (with predicted inhibition constant (Ki pred) = 177 μmol), HCQ = -5.7 kcal mol-1 (Ki pred = 64.07 μmol) and RDV -6.3 kcal mol-1 (Ki pred = 13.95 μmol). We got remarkable results for our docked ligands as 79% of total ligands indicated binding energies better than CQ, 39 % better than both HCQ and CQ, and 19 % better than all reference drugs. More interestingly interaction analysis of eight best-docked ligands showed that they interacted with desired key residues of Mpro. We further selected the four best-docked ligands L1 = -6.6 kcal mol-1 (Ki pred =13.95 μmol), L6 = -7.0 kcal mol-1 (Ki pred = 7.08 μmol), L34 = -6.0 kcal mol-1 (Ki pred = 38.54 μmol), and L50 = -6.6 kcal mol-1 (Ki pred =13.95 umol) for further analysis by quantum chemical study, molecular dynamic (MD) simulations and ADMET analysis. We have also carried out MD-simulations of six more docked ligand L2, L14, L20, L36, L46 and L48 some of which were showing weak binding affinities and some average binding affinities to check their simulation behavior. Their RMSD, RMSF and binding free energy results were also quite satisfying. We believe the current investigation will evoke the scientific community and highlights the potential of selected compounds for potential use as antiviral compounds against Mpro of SARS-CoV-2.

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Sweet, sour and bitter tasting fruits, vegetables and medicinal plants are an important component of human diet. The role of chromium and zinc in carbohydrate metabolism for control of diabetes is highlighted in selected commodities. Average levels of chromium and zinc in sweet taste were 0.69 ± 0.48 mg kg-1 and 4.81 ± 4.31 mg kg-1 respectively with correlation of 0.545, while in sour taste the values were 22.5 ± 22.0 mg kg-1 and 24.5 ± 11.8 mg kg-1 respectively with the correlation of 0.239 and in bitter taste, 0.61 ± 0.33 mg kg-1 and 4.70 ± 3.54 mg kg-1 respectively with correlation of 0.343. Overall, sour tasting commodities were found higher in levels of chromium and zinc and are recommended as food supplement for diabeties. None of these species contain metals above the toxic level.

The present investigation deals with the kinetics of submerged citric acid fermentation by Aspergillus niger using blackstrap molasses as the basal fermentation media. A laboratory scale stirred fermentor of 15-L capacity having working volume of 9-L was used for cultivation process and nutritional analysis. Among the 10 stock cultures of Aspergillus niger, the strain GCBT7 was found to enhance citric acid production. This strain was subjected to parametric studies. Major effects were caused due to oxygen tension (1.0 l/l/min), pH value (6.0) and incubation temperature (30ºC). All fermentations were carried out following the growth on 150 g/l raw molasses sugars for 144 hours. Ferrocyanide (200 ppm) was used to control the trace metals present in the molasses medium. Ammonium nitrate (0.2%) was added as nitrogen source. Maximum citric acid production (99.56 ± 3.5a g/l) was achieved by Aspergillus niger GCBT7. The dry cell mass and sugar consumption were 18.5 and 96.55 g/l, respectively. The mycelia were intermediate round pellets in their morphology. The specific productivity of GCBT7 (qp = 0.074 ± 0.02a g/g cells/h) was several folds higher than other strains. The specific production rate and growth coefficient revealed the hyperproducibility of citric acid using mutant GCBT7.

The present investigation deals with a novel technique for high and consistent yield of citric acid in a fed-batch bioreactor of 9-L working volume. Five different potent cultures of Aspergillus niger were evaluated for citrate production using clarified cane-molasses as basal substrate. Among the cultures, NG GCB101 (developed by UV/chemical mutation in our labs) gave maximum production of citric acid i.e., 87.98 g/l after 6 days of mycelial inoculation. The values of kinetic parameters such as substrate consumption and product formation rates revealed the hyperproducibility of citric acid by selected Aspergillus niger NG GCB101 (LSD = 0.456, HS). The addition of MnSO4 to the culture medium promoted the formation of small rounded fluffy pellets (1.55 mm², dia.), which are desirable for maximal citric acid productivity. During recycling fed-batch cultivation, high and consistent yield of citric acid monohydrate (128.68 g/l) was obtained when the sampling vs. substrate feeding was maintained at 4-L (44.50% working volume). The incubation period was reduced from 6 to only 2 days, making the process highly economical for citric acid production. MnSO4 at a level of 2.0 x 10-6 M, added during inoculation time optimised the commercial exploitation of molasses in recycling fed-batch cultivation system. The technique developed in the current studies is a new addition in fermentation technology due to high yields of product, recycling of the fermentation medium and fungal mycelia, low manpower and energy consumption and the use of low cost raw substrate without any additional supplementation.

Citric acid fermentation of cane-molasses by submerged fermentation in 15 L stirred fermentor (working volume 9 L) was carried out. A hyper mutant strain of Aspergillus niger GCMC-7 was used in the present study which was obtained from the culture collection of our own labs. Ferrocyanide treated molasses [K4Fe(CN)6 200 ppm] medium containing sugar 150 g/l was employed as the basal fermentation medium. Different cultural conditions such as incubation temperature (30ºC), initial pH (6.0), air supply (1.0 l-1l-1min), agitation intensity (200 rpm) and time profile (144 h after inoculation) were optimised for enhanced citric acid production. Maximum amount of anhydrous citric acid obtained during the course of study was 106.65 g/l, with a sugar consumption of 107 g/l. Final pH, ferrocyanide concentration and dry cell mass were 2.1, 60 ppm and 16.5 g/l, respectively.