PR-1-Like Protein as a Potential Target for the Identification of Fusarium oxysporum: An In Silico Approach

Fusarium oxysporum remains one of the leading causes of economic losses and poor crop yields; its detection is strained due to its presentation in various morphological and physiological forms. This research work sought to identify novel biomarkers for the detection of Fusarium oxysporum using in silico approaches. Experimentally validated anti-Fusarium oxysporum antimicrobial peptides (AMPs) were used to construct a profile against Fusarium oxysporum. The performance and physicochemical parameters of these peptides were predicted. The gene for the Fusarium oxysporum receptor protein PR-1-like Protein, Fpr1, was identified and translated. The resulting protein model from the translation was then validated. The anti-Fusarium oxysporum AMPs and Fusarium oxysporum receptor protein 3-D structures were characterized, and their docking interaction analyses were carried out. The HMMER in silico tool identified novel anti-Fusarium oxysporum antimicrobial peptides with good performance in terms of accuracy, sensitivity, and specificity. These AMPs also displayed good physicochemical properties and bound with greater affinity to Fusarium oxysporum protein receptor PR-1-like Protein. The tendency of these AMPs to precisely detect Fusarium oxysporum PR-1-like Protein, Fpr1, would justify their use for the identification of the fungus. This study would enhance and facilitate the identification of Fusarium oxysporum to reduce problems associated with poor crop yield, economic losses, and decreased nutritional values of plants to keep up with the growing population.

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

Concerns Raised on Blood Group Determinants in Plasma Membrane Interaction of the SARS-CoV-2

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

In silico approach: docking study of oxindole derivatives against the main protease of COVID-19 and its comparison with existing therapeutic agents

Objectives Presently, the pandemic of COVID-19 has worsened the situation worldwide and received global attention. The United States of America have the highest numbers of a patient infected by this disease followed by Brazil, Russia, India and many other countries. Moreover, lots of research is going on to find out effective vaccines or medicine, but still, no potent vaccine or drug is discovered to cure COVID-19. As a consequence, many types of research have designated that computer-based studies, such as protein–ligand interactions, structural dynamics, and chembio modeling are the finest choice due to its low cost and time-saving features. Here, oxindole derivatives have been chosen for docking because of their immense pharmacological applications like antiviral, antidiabetic, anti-inflammatory, and so on. Molecular docking of 30 oxindole derivatives done on the crystallized structure of the protein (COVID-19 Mpro). Methods The process of docking, interaction, and binding the structure of ligand with protein has executed using Molegro Virtual Docker v.7.0.0 (MVD) and visualized the usage by Molegro Molecular Viewer v.7.0.0 (MMV). Results Among the 30 derivatives, the outcomes depicted better steric interaction and hydrogen bonding amongst OD-22 ligand, OD-16 ligand, OD-4 ligand, and OD-9 ligand (oxindole derivatives) with COVID-19. In addition to this, the comparative study of these four compounds with existing drugs that are under clinical trials shows comparatively good results in terms of its MolDock scores, H-bonding and steric interactions. Conclusions Hence, It is proposed that these four oxindole derivatives have good potential as a new drug against coronavirus as possible therapeutic agents.

Computational modeling of AGO-mediated molecular inhibition of ARF6 by miR-145

Inhibition of ADP-ribosylation factor 6 messenger RNA (ARF6 mRNA) by microRNA-145 (miR-145), mediated by Argonaute (AGO) protein, has been found to play essential roles in several types of cancer and cellular processes. This study aimed to model the molecular interaction between miR-145 and ARF6 mRNA with AGO protein. The sequences of miR-145 and the 3’ untranslated region (UTR) of ARF6 mRNA were retrieved from miRTarBase, followed by miRNA target-site and structure predictions were done using RNAhybrid, RNAfold, and simRNAweb, respectively. The interaction between the miRNA-mRNA duplex and AGO was further assessed via molecular docking, interaction analysis, and dynamics, using PatchDock Server, PLIP, and VMD/NAMD, respectively. The models between miR-145, predicted target site of ARF6 mRNA, and AGO protein returned stable thermodynamic variables with negative free energy. Specifically, the RNA duplex had an energy of -19.80 kcal/mol, while the docking had -84.58 atomic contact energy supported by 70 hydrogen bonds and 14 hydrophobic interactions. However, the stability of the RMSD plot was still unclear due to limited computational resources. Nevertheless, these results computationally confirm favorable interaction of the three molecules, which can be utilized for further transcriptomics-based drugs or treatments.

Potential COVID-19 papain-like protease PLpro inhibitors: repurposing FDA-approved drugs

Using the crystal structure of SARS-CoV-2 papain-like protease (PLpro) as a template, we developed a pharmacophore model of functional centers of the PLpro inhibitor-binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. This search identified 147 compounds that can be potential inhibitors of SARS-CoV-2 PLpro. The conformations of these compounds underwent 3D fingerprint similarity clusterization, followed by docking of possible conformers to the binding pocket of PLpro. Docking of random compounds to the binding pocket of protease was also done for comparison. Free energies of the docking interaction for the selected compounds were lower than for random compounds. The drug list obtained includes inhibitors of HIV, hepatitis C, and cytomegalovirus (CMV), as well as a set of drugs that have demonstrated some activity in MERS, SARS-CoV, and SARS-CoV-2 therapy. We recommend testing of the selected compounds for treatment of COVID-19

Design, Synthesis and Biological Evaluation of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles and their Derivatives as Analgesic Agents

An efficient and environmental benign solvent-free synthesis of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles (4a-e) was accomplished by grinding 3-chloro-6-hydrazinopyridazine (2) and β-ketonitriles (3a-e) in the presence of p-toulenesulfonic acid as a catalyst. Subsequently, 6'-chloro group in 4a-e was replaced with cyclic 2° amine derivatives viz. pyrrolidine 5a, piperidine 5b and morpholine 5c to obtain 6a-e, 7a-e, 8a-e respectively. The newly synthesized compounds were characterized by using IR, NMR (1H and 13C), mass spectral studies, elemental analyses. All the synthesized compounds were studied for their docking interaction with target protein 6COX and screened for their in vivo analgesic mode of action against swiss albino mice (animal model) using acetic-acid induced writhing test. Consequently, docking simulations data justifies the potential of synthesized series as an analgesic and very well correlated with in vivo study. Preliminary results revealed that most of the synthesized compounds exhibited moderate to good analgesic activity as compared to reference/standard drug (s) sodium diclofenac and candidates 4d and 7c protrude out as a promising lead for further investigation.