Optimal Binding Features Research Articles

Molecular docking analysis of the oral tumor target JAK STAT 3 with oxo-azo compounds.

It is of interest to identify the JAK STAT 3 signaling inhibitors to abrogate tumorigenesis in oral cancer. Hence, molecular docking was performed with known oxazole compounds (1-5) and the 3D crystal structure of JAK-1 protein from Homo sapiens (PDB ID: 3EYG). The results show that the oxo-azo derivatives showed better interactions within the binding site of proteins. We report that compounds 1, 4 and 5 optimal binding features with JAK STAT 3.

Molecular docking analysis of Aza compounds with the heme-binding protein from Tannerella Forsythia.

The high biological activity and interesting optical properties of the aza compounds is known. Therefore, it is of interest to document the molecular docking analysis data of Aza compounds with the heme-binding protein from an anaerobic, Gram-negative bacterium Tannerella Forsythia. Hence, we report the optimal binding features of Aza compounds with the heme-binding protein from Tannerella Forsythia for further consideration in drug discovery against the pathogen.

Unsymmetrical aromatic disulfides as SARS-CoV-2 Mpro inhibitors: Molecular docking, molecular dynamics, and ADME scoring investigations

COVID-19 pandemic caused by very severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) agent is an ongoing major global health concern. The disease has caused more than 452 million affected cases and more than 6 million death worldwide. Hence, there is an urgency to search for possible medications and drug treatments. There are no approved drugs available to treat COVID-19 yet, although several vaccine candidates are already available and some of them are listed for emergency use by the world health organization (WHO). Identifying a potential drug candidate may make a significant contribution to control the expansion of COVID-19. The in vitro biological activity of asymmetric disulfides against coronavirus through the inhibition of SARS-CoV-2 main protease (Mpro) protein was reported. Due to the lack of convincing evidence those asymmetric disulfides have favorable pharmacological properties for the clinical treatment of Coronavirus, in silico evaluation should be performed to assess the potential of these compounds to inhibit the SARS-CoV-2 Mpro.In this context, we report herein the molecular docking for a series of 40 unsymmetrical aromatic disulfides as SARS-CoV-2 Mpro inhibitor. The optimal binding features of disulfides within the binding pocket of SARS-CoV-2 endoribonuclease protein (Protein Data Bank [PDB]: 6LU7) was described. Studied compounds were ranked for potential effectiveness, and those have shown high molecular docking scores were proposed as novel drug candidates against SARS-CoV-2. Moreover, the outcomes of drug similarity and ADME (Absorption, Distribution, Metabolism, and Excretion) analyses have may have the effectiveness of acting as medicines, and would be of interest as promising starting point for designing compounds against SARS-CoV-2. Finally, the stability of these three compounds in the complex with Mpro was validated through molecular dynamics (MD) simulation, in which they displayed stable trajectory and molecular properties with a consistent interaction profile.

Molecular docking analysis of FDA approved drugs with the glycoprotein from Junin and Machupo viruses.

Arenaviruses, Junin and Machupo are pathogenic viruses in regions of South America including Argentina and Bolivia causing haemorrhagic fever among humans. They have been transmitted to humans through mouse causing chronic illness with high mortality. Therefore, it is of interest to acquittance the molecular docking analysis data of FDA approved drugs with the glycoprotein from Junin and Machupo viruses for consideration in drug discovery. Thus, we report the optimal binding features of MK-3207 and Dihydro ergotamine with the protein target for further validation and consideration.

Molecular docking and simulation analysis of the FimH protein with secondary metabolites from the Garcinia species.

It is of interest to document the molecular docking and simulation analysis of the FimH protein with 10 secondary metabolites from Garcinia species in the context of drug discovery for Urinary tract infections (UTIs). We report the optimal binding features of flavonoids with the FimH protein for further consideration in drug discovery.

In silico study of six FDA approved anti-HCV drugs as inhibitors for NS5 methyltransferase of dengue virus type 2

Background & objectives: Dengue virus infection has become a major health threat. Dengue is a mosquito-borne viral infection caused by a viral RNA of the family Flaviviridae and spread by Aedes mosquitoes. Dengue NS5 methyltransferase is used as a drug target for the disease. Six FDA approved anti-HCV drugs were tested as potential dengue virus type 2 methyltransferase inhibitors using molecular docking analysis seeking potential treatment. Methods: Molecular docking analysis tested six FDA approved anti-HCV drugs, including Elbasvir, Daclatasvir, Ledipasvir, Pibrentasvir, Velpatasvir, and Ombitasvir. Results: 1000 ps molecular dynamics simulation of protein-complex validates its stability. Interpretation & conclusion: The analysis indicates the binding of Ombitasvir with the protein drug target with optimal binding features for further in vitro and in vivo evaluations. Ombitasvir was the optimum candidate ligand compound with binding affinity value (-11.56 ΁ 0.46 kcal/mol) with 2P3Q. Interactions of Ombitasvir with the active site residues of 2P3Q revealed good results for experimental drug testing.

Molecular docking analysis of bioactive compounds from Mollugo cerviana (L.) SER with DHFR for antifungal activity.

Fungal infections have been increasing in recent years due to growing number of high-risk patients particularly immuno compromised hosts. Candida is the third- or fourth-most-common isolate in nosocomial bloodstream infections. The increase of fungal resistance to classical drugs, the treatment costs, and the fact that most available antifungal drugs have only fungistatic activity, justify the search for new strategies. Identification of therapeutic compounds from plants has been the centre of attraction ever since they were discovered. It is of interest to document the molecular docking analysis of bioactive compounds present in Mollugo cerviana (L.) SER with the DHFR protein target for antifungal activity. We show the optimal binding features of several compounds from the extract with in vivo and in vitro activities. Results of this showed that all compounds showed good antimicrobial activity and a very good antifungal activity against the target DHFR protein. So, these compounds may act as potential drug molecules after the experimental validation.

Molecular docking analysis of glycogen phosphorylase with inhibitors from Cissampelos pareira Linn.

Cissampelos pareira Linn. is a climbing herb known in Indian traditional medicine as laghupatha. It belongs to the Menispermaceae family. The enzyme glycogen phosphorylase (GP) is a promising target for the treatment of type-2 diabetes (T2DM). A variety of natural product inhibitors with both pharmaceutical and nutraceutical potential have been reported in the search for powerful, selective and drug-like GP inhibitors that could lead to hypoglycemic medicines. Therefore, it is of interest to document the molecular docking analysis data of glycogen phosphorylase with compounds from Cissampelos pareira Linn. We report the optimal binding features of 4 compounds namely Trans-N-feruloyltyramine, Coclaurine, Magnoflorine, and Curine with the target protein for further consideration in the context of T2DM.

Molecular docking analysis of hyperphosphorylated tau protein with compounds derived from Bacopa monnieri and Withania somnifera.

Tau protein, the major player in Alzheimer’s disease forms neurofibrillary tangles in elderly people. Bramhi (Baccopa Monniera) is often used as an ayurvedic treatment for Alzheimer's disease. Therefore it is of interest to study the interaction of compounds derived from Baccopa with the Tau protein involved in tangle formation. We show that compounds such as bacopaside II, bacopaside XII, and nicotine showed optimal binding features with the R2 repeat domain of hyperphosphorylated tau protein for further consideration in the context of Alzheimer's disease (AD).

Molecular docking analysis of hyperphosphorylated tau protein with compounds derived from Bacopa monnieri and Withania somnifera

Tau protein, the major player in Alzheimer痴 disease forms neurofibrillary tangles in elderly people. Bramhi (Baccopa Monniera) is often used as an ayurvedic treatment for Alzheimer痴 disease. Therefore it is of interest to study the interaction of compounds derived from Baccopa with the Tau protein involved in tangle formation. We show that compounds such as bacopaside II, bacopaside XII, and nicotine showed optimal binding features with the R2 repeat domain of hyperphosphorylated tau protein for further consideration in the context of Alzheimer痴 disease (AD).

Molecular docking analysis of Clostridium perfringens beta toxin model with potential inhibitors from the ZINC database.

Beta toxin from Clostridium perfringens after being secreted in gut is capable of causing necrotic enteritis in humans and several other animal species and does not respond to routinely used antibiotics. Therefore, there is a need to design an effective inhibitor for the Clostridium perfringens beta toxin (CPB) using cutting edge drug discovery technologies. Hence, potential CPB inhibitors were identified using computer aided screening of compounds from the ZINC database. Further, we document the molecular docking analysis of Clostridium perfringens beta toxin model (that revealed 4 binding pockets, A-D) with the identified potential inhibitors. We show that ZINC291192 [N-[(1-methylindol-3-yl) methyl eneamino]-7,10-dioxabicyclo[4.4.0]deca-2,4,11-triene-8- carboxamide] has optimal binding features with calculated binding energy of -10.38 kcal/mol and inhibition constant of 24.76 nM for further consideration.

In silico molecular docking analysis for repurposing approved antiviral drugs against SARS-CoV-2 main protease

Developing a safe and effective antiviral treatment takes a decade, however, when it comes to the coronavirus disease (COVID-19), time is a sensitive matter to slow the spread of the pandemic. Screening approved antiviral drugs against COVID-19 would speed the process of finding therapeutic treatment. The current study examines commercially approved drugs to repurpose them against COVID-19 virus main protease using structure-based in-silico screening. The main protease of the coronavirus is essential in the viral replication and is involved in polyprotein cleavage and immune regulation, making it an effective target when developing the treatment. A Number of approved antiviral drugs were tested against COVID-19 virus using molecular docking analysis by calculating the free natural affinity of the binding ligand to the active site pocket and the catalytic residues without forcing the docking of the ligand to active site. COVID-19 virus protease solved structure (PDB ID: 6LU7) is targeted by repurposed drugs. The molecular docking analysis results have shown that the binding of Remdesivir and Mycophenolic acid acyl glucuronide with the protein drug target has optimal binding features supporting that Remdesivir and Mycophenolic acid acyl glucuronide can be used as potential anti-viral treatment against COVID-19 disease.

Molecular docking analysis of phytocompounds from Acacia farnesiana with protein targets linked to bronchitis.

Acute bronchitis is a lower respiratory tract lung infection that causes bronchial inflammation. The known protein drug targets are peptidoglycan D, D-transpeptidase, and DNA topoisomerase 4 subunit A for bronchitis linked infections. These are the membrane associated macromolecules which takes a major role in the formation of cell wall membrane by synthesising the cross-linked peptidoglycan. Therefore, it is of interest to design molecules with improved binding features with these protein targets. Hence, we document the molecular docking analysis data of four phytocompounds from Acacia farnesiana having optimal binding features with these targets linked to bronchitis for further consideration.

Molecular docking analysis of potential compounds from an Indian medicinal soup "kabasura kudineer" extract with IL-6.

The use of "kabasura kudineer" (liquid soup made from Indian medicinal plants) for combating COVID-19 has been common in the states of Tamilnadu and Puducherry, India during the pandemic. Therefore, it is of interest to document the molecular docking analysis of IL-6 inhibitors with potential antiviral compounds from "kabasura kudineer" extract. We show the optimal binding features of gallic acid and luteolin with the Interleukin-6 protein for further consideration.

Identification of aspirin and diclofenac binding proteins in the red complex pathogens.

Red complex organisms are a group of organisms (Porphyromonas gingivalis ATCC 33277, Treponema denticola ATCC 35405, Tannerella forsythia ATCC 43037) that have been identified for the causation of periodontal diseases. Aspirin and diclofenac have been used as regular analgesics. Therefore, it is of interest to document the identification of aspirin and diclofenac binding proteins in the red complex pathogens using the STITCH v.5 pipeline. The virulence properties of these proteins were analyzed using VICMPred and VirulentPred software. Thus, we document 000 number of proteins having optimal binding features with the known analgesics.

Molecular modeling of cornulin (CRNN) for docking with phytocompounds from Justicia adhatoda L.

Cornulin (CRNN) is linked with tumour progression. Therefore, it is of interest to document data on the molecular modeling of cornulin (CRNN) for docking with phytocompounds (Pyrazinamide, Anisotine, Vasicinone, Vasicoline) from Justicia adhatoda L. Thus, we document the optimal binding features of these compounds with the cornulin model for further consideration.

<i>In Silico</i> Analysis of ACE-2 and SARS-CoV-2 Spike (S) Glycoprotein with Known Phytocompounds from <i>Mammea Suriga</i> Kosterm

Design, screening and development of drugs to combat CoVid-19 is important during the viral outbreak. Therefore, it is of interest to document the molecular docking analysis data of ACE-2 and SARS-CoV-2 spike (S) glycoprotein with known phytocompounds from Mammea suriga in comparision with standard drug and tinosporin an antiviral phytocompound. We report the optimal binding features of, β-Sitosterol acetate, 1-acetyl-2,2,4-trimethyl-4-phenyl-1,2,3,4-tetrahydroquinoline, D-Homo-24-nor-17-oxachola-20,22-diene-3,16-dione,1,2:14,15:21,23-triepoxy-7-hydroxy, Taraxeron and Tinosporin with ACE-2 and SARS-CoV-2 spike (S) glycoprotein for further consideration. Funding: The authors are thankful to DBT, New Delhi, India, for providing financial support through the DBT-BUILDER program (Order No. BT/PR9128/INF/22/190/2013, Dated: 30/06/2015). Declaration of Interest: Authors state that there is no conflict of interest

Identification of protein targets in red complex organisms binding with resveratrol.

Periodontitis is attributed to the dental biofilm formation. Red complex organisms are a group of organisms linked with periodontal diseases. Therefore, it is of interest to identify potential targets from the red complex organisms to bind with the herbal compound resveratrol (E - 5 - (4 - hydroxy styryl) benzene 1,3 diol). We report a list of potential proteins having optimal drug like binding features with the herbal agent Resveratrol for further consideration. We used the STITCH v.5 pipeline VICMPred and VirulentPred tools to identify such targets as potential virulent factors in the red complex organisms. We considered the strains of Porphyromonas gingivalis ATCC 33277, Treponema denticola ATCC 35405 and Tannerella forsythia ATCC 43037 in the red complex pathogens for this analysis. Protein targets in the red complex organisms with optimal binding features with the herbal compound resveratrol were thus identified and reported for further consideration.

Molecular docking analysis of beta-catenin with compounds derived from Lycopersicon esculentum.

Beta-catenin is linked with colorectal cancer (CRC). Therefore, it is of interest to design and develop novel compounds to combat CRC. Hence, we document compounds (chlorogenic acid, gallic acid, protocatechuic acid, quercetin and vanillic acid) from Lycopersicon esculentum with optimal binding features for further consideration.

Molecular docking analysis of human JAK2 with compounds from tomatoes.

Janus kinase 2 (JAK2) is a tyrosine kinase receptor that belongs to the JAK family kinases is linked to oral cancer. We describe the molecular binding analysis of JAK2 with 23 compounds from tomotoes. Docking data shows five compounds (rutin, qucertin, narigenin, chlrogenia acid & kaempferol) with optimal binding features with JAK2 for further consideration.