Structural Modifications Introduced by NS2B Cofactor Binding to the NS3 Protease of the Kyasanur Forest Disease Virus.

Kyasanur Forest Disease virus (KFDV), a neglected human pathogenic virus, is a that causes severe hemorrhagic fever in humans. KFDV is transmitted to humans by the bite of the hard tick (), which acts as a reservoir of KFDV. The recent expansion of the endemic area of KFDV is of concern and requires the development of new preventive measures against KFDV.

Development of machine learning models based on molecular fingerprints for selection of small molecule inhibitors against JAK2 protein.

Janus kinase 2 (JAK2) is emerging as a potential therapeutic target for many inflammatory diseases such as myeloproliferative disorders (MPD), cancer and rheumatoid arthritis (RA). In this study, we have collected experimental data of JAK2 protein containing 6021 unique inhibitors. We then characterized them based on Morgan (ECFP6) fingerprints followed by clustering into training and test set based on their molecular scaffolds.

AlteQ: a new complementarity principle-centered method for the evaluation of docking poses.

Molecular docking is the most popular and widely used method for identifying novel molecules against a target of interest. However, docking procedures and their validation are still under intense development. In the present investigation, we evaluate a quantum free-orbital AlteQ method for evaluating docking complexes generated by taking EGFR complexes as an example.

A systems biology investigation of curcumin potency against TGF-β-induced EMT signaling in lung cancer.

Unlabelled: Curcumin (diferuloylmethane) is bioactive phenolic compound which exerts diverse antimetastatic effect. Several studies have reported the antimetastatic effect of curcumin by its ability to modulate the epithelial-to-mesenchymal transition (EMT) process in different cancers, but underlying molecular mechanism is poorly understood. EMT is a highly conserved biological process in which epithelial cells acquire mesenchymal-like characteristics by losing their cell-cell junctions and polarity.

Novel Insights into the Bioactive Metabolites of Macrocybe gigantea (Agaricomycetes), Using Gas Chromatography-Mass Spectrometry Combined with Chemoinformatic Approaches.

Macrocybe gigantea is an edible mushroom and has multiple pharmacological properties, including antibacterial, antioxidant, and antitumor activities. However, only a few reports are currently available on the bioactive compounds and bioactivity of this mushroom. Therefore, the present study aimed to explore the unique chemical diversity of the fruiting body of M.

Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer.

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity.

Exploring potential inhibitors against Kyasanur forest disease by utilizing molecular dynamics simulations and ensemble docking.

Kyasanur forest disease (KFD) is a tick-borne, neglected tropical disease, caused by KFD virus (KFDV) which belongs to (Flaviviridae family). This emerging viral disease is a major threat to humans. Currently, vaccination is the only controlling method against the KFDV, and its effectiveness is very low.

Proposition of a new allosteric binding site for potential SARS-CoV-2 3CL protease inhibitors by utilizing molecular dynamics simulations and ensemble docking.

The SARS-CoV-2 3CL protease (3CLpro) shows a high similarity with 3CL proteases of other beta-coronaviruses, such as SARS and MERS. It is the main enzyme involved in generating various non-structural proteins that are important for viral replication and is one of the most important proteins responsible for SARS-CoV-2 virulence. In this study, we have conducted an ensemble docking of molecules from the DrugBank database using both the crystallographic structure of the SARS-CoV-2 3CLpro, as well as five conformations obtained after performing a cluster analysis of a 300 ns molecular dynamics (MD) simulation.

Complementarity principle in terms of electron density for the study of EGFR complexes.

The complementarity principle is a well-established concept in the field of chemistry and biology. This concept is widely studied as the lock-and-key relationship between two structures, such as enzyme and ligand interactions. These interactions are based on the overlap of electron clouds between two structures.

Can natural products stop the SARS-CoV-2 virus? A docking and molecular dynamics study of a natural product database.

The SARS-CoV-2 3CLpro is one of the primary targets for designing new and repurposing known drugs. A virtual screening of molecules from the Natural Product Atlas was performed, followed by molecular dynamics simulations of the most potent inhibitor bound to two conformations of the protease and into two binding sites. Eight molecules with appropriate ADMET properties are suggested as potential inhibitors.

Computational insights into the binding mode of curcumin analogues against EP300 HAT domain as potent acetyltransferase inhibitors.

Acetylation plays a key role in maintaining and balancing cellular regulation and homeostasis. Acetyltransferases are an important class of enzymes which mediate this acetylation process. EP300 is a type 3 major lysine (K) acetyl transferase, and its aberrant activity is implicated in many human diseases.

Protein-protein Interaction and Molecular Dynamics of Iturin A Gene on Effector Proteins of Phytophthora infestans.

Aim And Objectives: Phytophthora infestans (Mont.) de Bary, the fungal pathogen causes late blight, which results in devastating economic loss among the Solanaceae. The bacillus lipopeptides show the antagonistic activity against the many plant pathogens, among bacillus lipopeptides reported as the antifungal gene.

Exploring the ethnomycological potential of Mont. through GC-MS and chemoinformatics tools.

Deciphering the ethnopharmacological importance is one of the prime steps towards understanding the indigenous traditional medicines practised over the centuries. With the advent of modern techniques, it is possible to unravel and explore the hidden ethnopharmacological benefits, comprising complex bioactive compounds of substantial health benefits and together it helps to treat the complex diseases without any side effects as seen in the case of modern synthetic drugs. In this concern, the present study aims to identify the ethnomycologically significant mycocompounds derived from the fruiting body of wild edible macrofungi, that contain a vast array of compounds with notable edibility and a wide spectrum of medicinal applications.

Network Pharmacology Approach Uncovering Pathways Involved in Targeting Hsp90 Through Curcumin and Epigallocatechin to Control Inflammation.

Aims: To fetch pathways involved in targetting Hsp90 through Curcumin and Epigallocatechin through Network pharmacological approach.

Background: Hsp90 is a molecular chaperone involved in stabilizing inflammatory protein which may lead to chronic diseases. The herbal compounds Curcumin and Epigallocatechin processing antiinflammatory properties are known to follow a common pathway and control the expression of Hsp90.

A systems biology approach to identify the key targets of curcumin and capsaicin that downregulate pro-inflammatory pathways in human monocytes.

VEGFR1 (Flt-1), is a high-affinity tyrosine kinase receptor of VEGF found primarily on vascular endothelial cells. Recently, Flt-1 has shown to be expressed in human monocytes. However, the key intracellular signaling pathway mediated by Flt-1 receptor has been yet to be identified in monocytes.

Exploring the Potential of Capsaicin Against Cancer Metastasis Based on TGF-β Signaling Modulation Through Module-based Network Pharmacology Approachx.

Background: Capsaicin is an active alkaloid /principal component of red pepper responsible for the pungency of chili pepper. Capsaicin by changing the intracellular redox homeostasis regulate a variety of signaling pathways ultimately producing a divergent cellular outcome. Several reports showed the potential of capsaicin against cancer metastasis, however unexplored molecular mechanism is still an active part of the research.

Molecular docking analysis of curcumin analogues against kinase domain of ALK5.

During metastasis, cancer cells transcend from primary site to normal cells area upon attaining epithelial to mesenchymal transition (EMT) causing malignant cancer disease. Increased expression of TGF-β and its receptor ALK5 is an important hallmark of malignant cancer. In the present study, efficacy of curcumin and its analogues as inhibitors of ALK5 (TGFβR-I) receptor was evaluated using in silico approaches.