There has recently been interest in the development of small-molecule inhibitors of the oligomerization of Bacillus anthracis protective antigen for therapeutic use. Some of the proposed lead compounds have, however, unfavorable solubility in aqueous medium, which prevents their clinical use. In this computational work, we have designed several hundreds of derivatives with progressively higher hydro-solubility

In the current work, the adsorption of sulfamide drug onto the exterior surface of four fullerene-like nanocages, including Al12N12, Al12P12, B12N12, and B12P12, was studied by employing density functional theory (DFT) and the quantum theory of atom in the molecule (QTAIM) calculations. Our calculations revealed that the sulfamide drug connects to the Al, B, P, and N atoms of Al12N12, Al12P12, B12N12

Abstract A computational approach to in silico drug discovery was carried out to identify small drug-like compounds able to show structural and functional mimicry of the high affinity ligand X77, potent non-covalent inhibitor of SARS-COV-2 main protease (MPro). In doing so, the X77-mimetic candidates were predicted based on the crystal X77-MPro structure by a public web-oriented virtual screening platform

Fas-activated serine/threonine kinase (FASTK) is a mitochondria-associated nuclear protein that inhibits Fas- and UV-induced apoptosis. This protein is generally activated during Fas-mediated apoptosis by phosphorylating a nuclear RNA-binding protein T-cell intracellular antigen-1 and thus considered as a modulator of apoptosis. In the present study, we have examined the equilibrium unfolding and conformational

Hydrogen bonding between amino acids and nucleobases is important for RNA–protein recognition. As a first step toward understanding the physicochemical features of these contacts, the present work employs density functional theory calculations to critically analyze the intrinsic structures and strength of all theoretically possible model hydrogen-bonded complexes involving RNA nucleobase edges and

Non-structural protein 1 (nsp1) is found in all Betacoronavirus genus, an important viral group that causes severe respiratory human diseases. This protein has significant role in pathogenesis and it is considered a probably major virulence factor. As it is absent in humans, it becomes an interesting target of study, especially when it comes to the rational search for drugs, since it increases the

The compounds 7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (5) and 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione (7), were synthesized from dimedone and barbituric acid and had their three-dimensional structures and precise chemical shifts assignments obtained by Nuclear Magnetic Resonance

Letrozole and metronidazole are two commonly used drugs for the management of breast cancer and parasitic infections, respectively. This manuscript attempts to study their structure, geometry, search for stable conformers using relaxed potential energy scan, spectral properties, quantum mechanical properties like energy and reactivity descriptors, intra molecular electron transfer properties, non-linear

Androgens and androgen receptors (AR) are the master regulators in the development of prostate cancer. Majority of the patients show positive response to surgical or medical castration, while many patients show disease relapse after the treatment. Genomic profiling has proven that the deregulated PI3K, Ras/Raf, MAPK and EGFR signaling pathways confer survival and invasion advantage to the cancer cells

Abstract We propose here that one of the potential mechanisms for the relapse of the COVID-19 infection could be a cellular transport pathway associated with the release of the SARS-CoV-2-loaded exosomes and other extracellular vesicles. It is possible that this “Trojan horse” strategy represents possible explanation for the re-appearance of the viral RNA in the recovered COVID-19 patients 7–14 day

SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use

The proteins encoded by the two major breast cancer genes (BRCA1 and BRCA2), ensure the stability of DNA and prevent uncontrolled cell growth; mutation of these genes is linked to the development of hereditary breast cancers. Exploration of human breast cancer inhibitors plays a vital role in the drug discovery process. In the current work, in silico studies were performed which involves a computational

The sharp spurt in positive cases of novel coronavirus-19 (SARS-CoV-2) worldwide has created a big threat to human. In view to expedite new drug leads for COVID-19, Main Proteases (Mpro) of novel Coronavirus (SARS‐CoV‐2) has emerged as a crucial target for this virus. Nitric oxide (NO) inhibits the replication cycle of SARS-CoV. Inhalation of nitric oxide is used in the treatment of severe acute respiratory

All over the world, diabetes mellitus type 2 has spread as a problematic pandemic. Despite currently available treatments, approved drugs still show undesirable side effects and loss of efficacy or target symptoms instead of causes. Protein tyrosine phosphatase 1B (PTP1B), since its discovery, has emerged as a very promising target against this disease. Although the information regarding the enzyme

Abstract In December 2019, a COVID-19 epidemic was discovered in Wuhan, China, and since has disseminated around the world impacting human health for millions. Herein, in-silico drug discovery approaches have been utilized to identify potential natural products (NPs) as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) inhibitors. The MolPort database that contains over

The signaling response of TLR2 to ligands has always been as a homodimer or in heterodimerization with TLR1/TLR6. The Toll/Interleukin-1 Receptor (TIR) domain of the TLR cytoplasmic region regulates the dimerization and interactions with adaptor molecules to build an active signaling complex. To understand the conservation of functionality of the TLR2-heterodimers between the distantly related species

Calcium Dependent Protein Kinases are found in the Apicomplexan, algae, and plants; however, they are reported in vertebrates and are regarded as excellent drug targets for pharmaceutical interventions. Calcium Dependent Protein Kinases of Cryptosporidium are probably involved in the regulation of invasion and egress process during the infection of the host cells. The previous study reported that after

(2020). Correction notice. Journal of Biomolecular Structure and Dynamics. Ahead of Print.

In the present study, we explored phytochemical constituents of Tinospora cordifolia in terms of its binding affinity targeting the active site pocket of the main protease (3CL pro) of SARS-CoV-2 using molecular docking study and assessed the stability of top docking complex of tinosponone and 3CL pro using molecular dynamics simulations with GROMACS 2020.2 version. Out of 11 curated screened compounds

Initially, the SARS-CoV-2 virus was emerged from Wuhan, China and rapidly spreading across the world and urges the scientific community to develop antiviral therapeutic agents. Among several strategies, drug repurposing will help to react immediately to overcome the COVID-19 pandemic. In the present study, we have chosen two clinical trial drugs against HIV-1 protease namely, TMB607 and TMC310911 to

Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates integrin and growth factor signaling pathways, which is a promising therapeutic target because of involving in the migration, proliferation and survival of cancer cell. Overexpression and amplification of cyclin-dependent kinase 4/6 (CDK4/6) occur in many cancers and may be the cause of resistance to CDK4/6 inhibitors in preclinical

Abstract Deep learning models are widely used in the automatic analysis of radiological images. These techniques can train the weights of networks on large datasets as well as fine tuning the weights of pre-trained networks on small datasets. Due to the small COVID-19 dataset available, the pre-trained neural networks can be used for diagnosis of coronavirus. However, these techniques applied on chest

Interferon regulatory factor 1 (IRF-1) plays a vital role in cell proliferation and cell differentiation by acting as a tumor suppressor gene and its role is linked to various types of cancers, including leukemia and pre-leukemia myelodysplasia. Mutations in the coding region of the IRF-1 are likely to influence the IRF-1 and its DNA binding affinity. The molecular mechanism of the DNA recognition

The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CLpro and PLpro

World is witnessing exponential growth of SARS-CoV2 and fatal outcomes of COVID 19 has proved its pandemic potential already by claiming more than 3 lakhs deaths globally. If not controlled, this ongoing pandemic can cause irreparable socio-economic and psychological impact worldwide. Therefore a safe and effective vaccine against COVID 19 is exigent. Recent advances in immunoinformatics approaches

In present work, we describe a methodology for prediction of an enzymatic reaction for which no experimental data are available except for a gene sequence. As a challenging case, we have developed the method for identifying the putative substrates of monoester phosphatases, commonly known as acid phosphatase enzymes, which have no strong substrate specificity. Finding a preferable substrate for each

The recent outbreak of the 2019 novel coronavirus disease (COVID-19) has been proved as a global threat. No particular drug or vaccine has not yet been discovered which may act specifically against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and causes COVID-19. For this highly infectious virus, 3CL-like main protease (3CLpro) plays a key role in the virus life cycle and can be considered

The mutations concerned with non-small cell lung cancer involving epidermal growth factor receptor of tyrosine kinase family have primarily targeted. EGFR inhibitors binding allosterically to C797S mutant EGFR enzyme have been developed. Here, database building, library screening performing R-group enumeration and scaffold hopping technique for increasing the EGFR binding affinity of compounds have

P-glycoprotein (P-gp, MDR1), one of ATP-binding cassette transporters, may confer tumor cells cross-resistance to chemotherapeutics. A large amount of P-gp inhibitors were designed to inhibit the multidrug resistance (MDR) feature of P-gp. However, no sufficient researches were reported to explore the correlation between binding capacity and drug property by experiment. Without particular drug property

Docetaxel (DOX) based combination therapy is a novel therapeutic strategy that attracts great interest in breast cancer treatment but its clinical utility got limited due to side effects. In contrast, noscapine, an antitussive drug showed antitumor activity against many cancers without any side effects that targets microtubules and attenuates its dynamic instability. In the quest for an increase in

Prunus amygdalus (PA) is a popular invasive seed utilized in the management of diabetes in Jammu and Kashmir, India. The objective of the current study was to scrutinize the antidiabetic effect of Prunus amygdalus (PA) against Streptozotocin (STZ) induced diabetic rats and explore the possible mechanism of action at cellular and sub-cellular levels. Box Benkan Design (BBD) was performed to determine

Quantitative Structure Activity Relationship (QSAR) is one of the realistic and most successful methods for drug design in optimizing a lead. A series of forty-four molecules from diarylpyrazole benzene sulphonamide derivatives with their cyclooxygenase-2 inhibitory activity were subjected to qsar studies using QSARINS software. The significant two descriptor qsar model generated showed correlation

Culex quinquefasciatus Cqm1 protein acts as the receptor for Lysinibacillus sphaericus mosquito-larvicidal binary (BinAB) toxin that is used worldwide for mosquito control. We found amino acid transporter protein, rBAT, as phylogenetically closest Cqm1 homolog in humans. The present study reveals large evolutionary distance between Cqm1 and rBAT, and rBAT ectodomain lacks the sequence motif which serves

A sequence of aroyl selenourea ligands (L1–L3) substituted by aniline and their Ru(II) (η6-p-cymene) complexes (1-3), [Ru(II) (η6-p-cymene) L] (L = monodentate aroyl selenourea ligand) have been synthesized and characterized the composition of the ligands and their metal complexes. The molecular structures of ligand L1 and complex 3 were also confirmed by single XRD crystal method. The single-crystal

A mononuclear nickel(II) complex, [Ni(o-van-tris)2]·2H2O (o-van-tris = Schiff base derived from o-vanillin and tris(hydroxymethyl)aminomethane), has been synthesized and structurally characterized. The single crystal structure shows a distorted octahedron geometry coordinated with Ni(II) atom, and 2 D plane structure has formed by O–H···O hydrogen bond interactions. An analysis to ascertain intermolecular

SARS-CoV-2 or Coronavirus disease 19 (COVID-19) is a rapidly spreading, highly contagious, and sometimes fatal disease for which drug discovery and vaccine development are critical. SARS-CoV-2 papain-like protease (PLpro) was used to virtually screen 1697 clinical FDA-approved drugs. Among the top results expected to bind with SARS-CoV-2 PLpro strongly were three cell protectives and antioxidants (NAD+

In this work, the new diaminochromenes: 2,5-dimono-8-methoxychromeno[4,3,2-de][1,6]naphthyridine-4-carbonitrile (4), 8-ethoxy-2-imino-3,4-dihydro-2H-chromene-3-carbonitrile-4-malononitrile (5), 2,5-diamino-8-ethoxychromene[4,3,2-de][1,6]naphthyridine-4-carbonotrile (6), were synthesized and fully characterized through 600 MHz using 1H, 13C, APT, gHSQC, gHMBC, ROESY-1D and gated decoupling 13C. Further

Lamellar ichthyosis (LI) is a rare inherited disease where affected infants present a extensive skin scaling characterized by hyperkeratosis. Inherited mutations in the Transglutaminase 1 (TGM1) protein is one of the known causative genetic factor for the LI. The main objective of this study is to explore the impact of LI causative missense mutations on the structural and stability aspects of TGM1

Polyamine synthesis in human cells is initiated by catalytic action of Ornithine decarboxylase (ODC) on Ornithine. Elevated levels of polyamines are manifested proliferating cancer cells and are found to promote tumour cell adhesion. Di-flouro methyl orninthine is a known inhibitor of ODC, however its usage is limited due its low affinity quick clearance and incompetent cellular uptake, thus posing

The Transforming growth factor-beta (TGFβ) superfamily is a group of multipotent growth factors that control proliferation, quiescence and differentiation. Aberrant signal transduction and downstream target activation contribute to tumorigenesis and targeted therapy has therefore been considered a promising avenue. Using various modeling pipelines, we analyzed the structure-function relationship between

Selective monoamine oxidase-B (MAO-B) inhibition is an attractive subject for the treatment of Parkinson’s disease (PD). In the current study, we synthesized some selected derivatives of methylthiosemicarbazones and investigated their MAOs and acetylcholinesterase (AChE) inhibitory activities. Among the series synthesized, compounds SM5, SM4, and SM9 most inhibited MAO-B with IC50 values of 5.48, 7

In this study, the spectroscopic methods (UV–vis, fluorimetric), Atomic force microscopy, and computational studies (molecular docking and molecular dynamic simulation) were used to investigate the interaction of [SnMe2Cl2(Me2phen)] complex with CT-DNA in the presence of glucose. The results showed the complex in the medium containing glucose has less effect on calf thymus DNA (ct-DNA) than the medium

Alzheimer’s disease (AD) is a growing global health concern that affects 10% of the population aged above 65 years. A growing body of evidence indicates that multi-targeted drugs might be useful therapeutic options owing to the heterogeneity of AD pathology. The current study exploited advanced computational biology tools to identify ligands that might display effective binding to two protein targets

The Coronavirus disease named COVID-19 is caused by the virus reported in 2019 first identified in China. The cases of this disease have increased and as of June 1st, 2020 there are more than 216 countries affected. Pharmacological treatments have been proposed based on the resemblance of the HIV virus. With regard to prevention there is no vaccine, thus, we proposed to explore the spike protein due

The apolipoprotein E (APOE) involved in lipid metabolism participates in the clearance and deposition of the amyloid-beta peptide of the Alzheimer’s disease (AD). The isoform APOE4 with the ARG112 mutation is the main genetic risk for the late-onset AD. Herein, using both molecular dynamics and quantum mechanics, the binding mechanisms of APOE4 leading to the AD are unraveled and now available for

G Protein-Coupled Receptor gains more importance in cancer research; because of their key role in several physiologic functions of cells. However, most of the GPCR’s are orphan receptors, this hampers the finding of drugs against GPCR. G Protein-Coupled Receptor 116 is an adhesion orphan receptor that intensifies the invasion of cells in Triple-Negative Breast Cancer. In this study, existing FDA approved

Overexpression of E26 transformation-specific (ETS) PEA3 subfamily transcription factor (TF) ETV1 is reportedly oncogenic and metastatic in several cancers. Albeit, a few synthetic small molecule inhibitors of ETV1 have been identified to date. In this context, we hereby proposed a phytochemical lead development scheme to gather inhibitor scaffolds for ETV1. A fingerprint-based similarity search was

β-Lactoglobulin (β-LG) is a member of lipocalin superfamily of transporters for small hydrophobic and hydrophilic molecules. We located the binding sites of citric acid and gallic acid on β-lactoglobulin (β-LG) in aqueous solution at physiological conditions, using spectroscopic methods, thermodynamic analysis and molecular modeling. Thermodynamic parameters ΔH0 −9.5 to −6.9 (kJ mol−1), ΔS0 23.9 to

Communicated by Ramaswamy H. Sarma

Recent studies reported the association of the Zika virus (ZIKV) with a stress response receptor on the host cell membrane that facilitates viral entry. This host receptor was the heat shock protein A5 (HSPA5), also termed glucose-regulating protein 78 (GRP78). In this study, structural bioinformatics and molecular dynamics simulations were utilized to suggest the binding site of ZIKV envelope protein

Lung cancer ranks number one among the all cancer types in the world, out of which 85% are non-small cell lung cancer (NSCLC). In case of NSCLC, a substitution mutation of Leu 858 Arg (L858R) in the gene of Epidermal Growth Factor Receptor (EGFR) has been reported. Hence, targeting EGFR containing L858R mutation using inhibitors is well reported strategy to discover potential drugs against NSCLC. The

Abstract COVID-19 has ravaged the world and is the greatest of pandemics in human history, in the absence of treatment or vaccine the mortality and morbidity rates are very high. The present investigation was undertaken to screen and identify the potent leads from the Indian Ayurvedic herb, Asparagus racemosus (Willd.) against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis

Emerging cases of drug resistance against Artemisinin combination therapies which are the current and the last line of defense against malaria makes the situation very alarming. Due to the liability of single-target drugs to be more prone to drug resistance, the trend of development of dual or multi-target inhibitors is emerging. Recently, a malaria box molecule, MMV007571 which is a well known new

Human African trypanosomiasis (HAT) or sleeping sickness like infections remain a serious health concern around the globe due to unavailability of safe and potential drugs for their treatment. Moreover, developing safe, potential and highly specific target based treatments is still a challenge for present drug discovery programs. A series of pyrazole based sulfonamides are identified as an inhibitor

In this study, five new complexes containing deferiprone (dfp) and N,N-donor ligands [bipyridine (bpy), 1,10-phenanthroline (phen) and ethylenediamine (en)] were synthesized: [Fe(dfp)2(bpy)](PF6) (1), [Fe(dfp)2(phen)](PF6) (2), [Cu2(dfp)2(bpy)2](PF6)2 (3), [Ga(dfp)2(bpy)](PF6) (4), and [Fe(dfp)2(en)](PF6) (5). Characterization of these complexes was carried out through elemental analysis and FT-IR

Caulerpin, a bis-indole alkaloid is isolated from a new source Sargassum platycarpum, brown alga (family Sargassaceae) for the first time. The structure of caulerpin was characterized by IR, H1NMR, C13 NMR, HSQC, HMBC, EI-MS spectroscopy. Antifungal results suggest that caulerpin has been inhibited Cryptococcus neoformas (12 mm) and Candida albicans (7 mm) than other microbes. In vitro anticancer activity

Application of proteinous drugs can be associated with difficulties during both in storage/transportation and in the body when they are used. However, using pharmaceutical carbohydrates that are widely employed in drug delivery systems, besides the drug can be protected, these systems leading to gradually release the drug over time, or deliver it to the target cell. Using a combination of molecular

The SARS-CoV-2 was confirmed to cause the global pandemic of coronavirus disease 2019 (COVID-19). The 3-chymotrypsin-like protease (3CLpro), an essential enzyme for viral replication, is a valid target to combat SARS-CoV and MERS-CoV. In this work, we present a structure-based study to identify potential covalent inhibitors containing a variety of chemical warheads. The targeted Asinex Focused Covalent

Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities’ world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time screening was performed

Pancreatic ductal adenocarcinoma (PDAC) is a major health issue that has been eluding efforts to identify viable therapeutic treatment options. Besides having the lowest survival rate among all types of cancer, almost all conventional methods of treatment are futile against this condition, leaving patients to succumb to this ailment faster than ever. As it is increasingly becoming difficult to come