MOLECULAR DOCKING OF GANOMESTENOL WITH SARS-COV-2 MPRO

Objective: The present study focused on binding mode of the N3 inhibitor and Ganomestenol with receptor SARS-CoV-2 Mpro protease. Methods: The structure of ligands N3 inhibitor and Ganomestenol were designed and 3-D coordinates were prepared using ACD/ChemSketch 8.0 freeware. Autodock4 software was used to study the orientation of the inhibitor or ligand in the active site of biological receptor SARS-CoV-2 Mpro (PDB ID: 6LU7). The Lamarckian genetic algorithm was applied to both ligand and protein for energy minimization using default parameters. The results were analyzed by Ligplot and Pymol software. Results: The compound Ganomestenol designed in in-silico for molecular docking with SARS-CoV-2 protease (Mpro). The in-silico results showed significant binding energy (−6.93 kcal/mol) by comparing with N3 inhibitor (−3.51 kcal/mol). Conclusion: The affinity of Ganomestenol is highly significant compared to N3 inhibitor and also showed efficacy of ligand toward protease under in-silico condition

TiPs: A database of therapeutic targets in pathogens and associated tools

Motivation: The need for new drugs and new targets is particularly compelling in an era that is witnessing an alarming increase of drug resistance in human pathogens. The identification of new targets of known drugs is a promising approach, which has proven successful in several cases. Here, we describe a database that includes information on 5153 putative drug-target pairs for 150 human pathogens derived from available drug-target crystallographic complexes. © 2013 The Author 2013. Published by Oxford University Press. All rights reserved.The need for new drugs and new targets is particularly compelling in an era that is witnessing an alarming increase of drug resistance in human pathogens. The identification of new targets of known drugs is a promising approach, which has proven successful in several cases. Here, we describe a database that includes information on 5153 putative drug-target pairs for 150 human pathogens derived from available drug-target crystallographic complexes

Uji Efek Inhibitorik Komponen Bioaktif Bawang Putih (Allium sativum) terhadap Lanosterol 14α-demethylase pada Candida albicans melalui Studi In Silico

Candida albicans is a unicellular fungi which causes candidiasis in human and livestock animals especially chicken. Candidiasis could reduce productivity significantly by early culling and causing a great deficit in the farm. Allium sativum or garlic is widely known as herbal which has an inhibitory effect in fungi’s growth. This research’s aim is to prove the effectivity of bioactive compound in Allium sativum to lanosterol 14α-demethylase which plays a role in ergosterol synthesis as a basic structure in fungi’s cell membrane. The ligand sheet retrieved from PubChem database and for the receptor in Protein Data Bank database. Molecular docking conducted by using Autodock Vina and then ligand-receptor complex is visualized with PyMOL and Ligplot+. From compounds that we have been analyzed, Gallic Acid has the most negative binding energy than other compounds have and it has the same amino acid residue with control. In conclusion of that, Gallic Acid in Allium sativum has potential as anti-candidiasis drug

COMPARISON OF COMMERCIALLY AVAILABLE DRUGS FOR TYPE 2 DIABETES WITH NATURAL MOLECULE FROM TINOSPORA

Objective: Efficacy of natural molecule from Tinospora cordifolia versus commercially available drugs to control diabetes 2.Methods: Twelve different drug molecules were selected to study drug properties, bioactivity and detailed mode of action. A comparative study was carried out among the drugs and plant metabolite to understand the putative mechanism of metabolite action and its potential to be developed as an herbal drug. PharmaGist Server was used to carry out pharmacophore modeling. The sequence of the target molecule (Q09428) was retrieved from UniProtKB/SwissProt, and structure prediction was carried out using ITASSER. The best model generated was further refined by energy minimization using Deep View. Validation of the structure was performed by Ramachandran plot analysis using PDBSum. Interaction analysis of the docked complex was done using LigPlot+.Results: The potential of natural plant metabolite to target ATP-binding cassette sub-family C member 8 seems probable based on docking and interaction analysis results. The natural molecule showed comparable binding energy (-5.57) in four out of seven drugs.Conclusion: Natural molecule from Tinospora cordifolia may serve as a potential lead drug molecule after modification and optimization for enhanced interaction.Keywords: Diabetes mellitus, Natural molecule, Tinospora, Type 2 diabete

Evaluation of COVID-19 protease and HIV inhibitors interactions

The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites

Biogenic Synthesis and antibiofilm efficacy of iron nanoparticles via computer simulation

The search for new drugs can be accelerated by in silico methods, i.e., fully computational methods known for their speed and low cost, allowing the analysis of a large amount of data, e.g., thousands of possible antimicrobials, in a few weeks. Molecular docking and first-principles calculations are great allies in this quest. They enable the assessment of protein-ligand interactions and can predict interactions between NPs and macromolecules to provide more information about the interactions and dynamics of NPs in biological systems. In this context, this work aims to use in silico methods to detect the formation of biogenic metallic nanoparticles from functional microalgal biomolecules of the genus Chlorella, which have chelation of metal ions as a fundamental property, and to verify the possible antibacterial biofilm efficacy using computational tools such as molecular docking. In a first analysis, it was found that the iron salt FeSO4 was the most suitable to bind the microalgal enzyme and produce its phytochelatin protein. Following this result, an analysis of the electronic structure of the phytochelatin complex with the iron salt was carried out, proving its structural modification at the nanometric level, after which an analysis of its therapeutic effect on antibiofilm activity was performed. S. aureus, a bacterium known for its multiresistant to antibiotics, these results demonstrate, through alternative in silico methods, the physiological role of phytochelatin from microalgae in the detoxification and bioremediation of metallic contaminants

Phosphodiesterase-1 Inhibitory Activity of Two Flavonoids Isolated from Pistacia integerrima J. L. Stewart Galls.

Pistacia integerrima is one of twenty species among the genus Pistacia. Long horn-shaped galls that develop on this plant are harvested and used in Ayurveda and Indian traditional medicine to make “karkatshringi”, a herbal medicine used for the treatment of asthma and different disorders of respiratory tract. However, until now, the molecular mechanisms of action of “karkatshringi” and its chemical characterization are partially known. This study deals with the isolation and characterization of the active constituents from the methanolic extract of P. integerrima galls and it was also oriented to evaluate in vitro and in silico their potential enzymatic inhibitory activity against phosphodiesterase-1 (PDE1), a well-known enzyme involved in airway smooth muscle activity and airway inflammation. Our results showed that the methanolic extract of P. integerrima galls and some of its active constituents [naringenin (1) and 3,5,7,4′-tetrahydroxy-flavanone (2)] are able in vitro to inhibit PDE1 activity (59.20 ± 4.95%, 75.90 ± 5.90%, and 65.25 ± 5.25%, resp.) and demonstrate in silico an interesting interaction with this enzymatic site. Taken together, our results add new knowledge of chemical constituents responsible for the biological activity of P. integerrima and contextually legitimate the use of this plant in folk medicine